Kojic Acid Research Papers - Academia.edu (original) (raw)

Kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) is a common contaminant of many food products which are part of humans or animals daily nutrition (sake, soy sauce, cereals, fodder and dairy products). This mycotoxin has demonstrated antibacterial, antifungal, antiparasitic, insecticide, antioxidant and skin whitening effects. In this study, adult zebrafish were divided in 4 groups: Control and 3 kojic acid-treated groups which were exposed to 100 mg/l, 204 mg/l and 284 mg/l kojic acid for 7 days. Histological alterations of the control and kojic acid-treated group were examined and compared, with emphasis on liver, kidney, pancreas, intestine, brain and myocardium. While the Control group had no histological alterations, the kojic acid-exposed zebrafish show hepatocytes hyperhydration/vacuolation, fragmentation of the cell membrane, nuclear karyolysis/pycnosis, a significant shortening of the intestinal villi, myocardiocytes degeneration, a moderatesevere myocardial congestion, an important lipid infiltration of the exocrine pancreas leading to the atrophy of the acini, nephrocyte degeneration and hyalinosis, nuclear hyperhydration, reduction to annulation of the tubular lumens. The histological alterations increase proportionally with the kojic acid dose.

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- Ichthyology, Toxicology, Fish Biology, Histology

- by T-L Mandalian and +1
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- Statistics, Machine Learning, Toxicology, Statistical Analysis

To maximize kojic acid production by AspergiZlusflavus Link 44-1 using gelatinized sago starch as a carbon source, the performance of different fermentation modes (batch and fed-batch with different feeding modes) was investigated in an 8-t stirred tank fermentor. The addition of a large volume of concentrated sago starch (140 g/r) 2 d after the start with an initial starch concentration of 60 g/;l produced the maximum concentration of kojic acid (16.43 g/l), which was about 4 times higher than that for batch fermentation of 100 g/l sago starch. Further improvement of kojit acid p~du~tion was obtained by adding small amounts of concentrated starch (140 g/l) intermi~ently at 2-d intervals to the culture. Using this technique of fermentation, the dissolved oxygen tension (DOT) can be controlled at high levels (40-50% saturation) during the active growth phase, which is required for the enhanced secretion of a-amylase used for saccharification of starch and also for the production of mycelia with higher ability in synthesizing kojic acid. Maintaining the culture pH at 3 throughout the intermittent fed-batch fermentation reduced kojic acid production (7.26 g//) significantly. Very little kojic acid (0.93 g/c) was produced when the pH was kept at 4 during the growth phase and then lowered to 3 during the production phase. A high level of kojic acid production (31.OOgll) was achieved in fermentation where the pH was not controlled throughout the cultivation or not controlled during the growth phase but kept at 3 during the production phase. This result indicates that the pH control strategy is important; with the variation in culture pH during the growth phase beiug most significant and critical to kojic acid production. [

- by Mohd Hassan
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- Engineering, Technology, Bioscience, Biological Sciences

With the aim to design new chelators for the clinical treatment of different diseases involving the trivalent metal ions Fe(III) and Al(III), we present the equilibria of kojic acid and its derivative 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyran-4-one with these two metal ions. Potentiometric and spectrophotometric techniques for iron, and potentiometry and (1)H NMR for aluminum were used, supported by X-ray, electrospray ionization-mass spectrometry (ESI-MS), calorimetry and quantum chemical calculations. In this work, evidence is given on the formation of MeL, MeL(2), and MeL(3) complexes of both metal ions with kojic acid, confirmed by the X-ray structure of the FeL(3) complex, and of variously protonated Me(2)L(2) and MeL(2) complexes of 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyran-4-one. The extremely good pFe value for this second ligand gives confidence to, and opens perspectives for, the search of new kojic acid deriv...

- by Maurizio Remelli and +5
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- Thermodynamics, Inorganic Chemistry, Inorganic, Molecular modeling

Growth and kojic acid production by Aspergillus flavus Link 44-1 were studied at difSerent levels of dissolved oxygen tension (DOT) using a 2-1 stirred tank fermenter. In all experiments, agitation was fixed at 600 rpm and DOT was controlled at different levels by varying airflow rates. Single-phase DOT control at three different levels (30, SO, and 80% saturation) did not enhance kojic acid production when compared to fermentation without DOT control (13.5 g 1-t). The production of kojic acid in a fermentation with single-phase DOT control at 80'S was comparable to that of a fermentation without DOT control. Decreased DOT levels below 80% reduced the production of kojic acid significantly although the biomass increased. When DOT was controlled at a very high level (80%) during active growth and then decreased to a low level (30%) during the production phase (i.e., two-phase DOT control), the production of kojic acid (28.9 g I-') was increased by about two times compared to a fermentation without DOT control; however, when yeast extract was added continuously in a fermentation with two-phase DOT control, active growth occurred during the production phase and the maximum accumulation of kojic acid was reduced significantly. High DOT during on active growth phase and no addition of yeast e.xtract during the production phase were required to enhance kojic acid biosynthesis. The most effective control strategy for kojic acid production, therefore, was to control DOT at very high levels during active growth and not add a nitrogen source during the production phase while using low levels of DOT. 0 1996 by Elsevier Science Inc.

- by Ismail Abdul Hassan
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- Environmental Biotechnology, Kojic Acid, Nitrogen, Aspergillus flavus

In this study, the effect of different anti-browning agents on the enzymatic browning in the cloudy apple juice from Amasya cultivar was compared by considering colour changes. For this purpose, L L -cysteine, kojic acid and 4-hexylresorcinol were used at different concentrations in the apple juice (0-4 mM). They were found as effective inhibitors. The combination of L L -cysteine, kojic acid and 4-hexylresorcinol was also studied for the control of enzymatic browning. The results showed that 89.2% inhibition was obtained at the end of 24 h storage period with the combination of 3.96 mM L L -cysteine, 2.78 mM kojic acid and 2.34 mM 4-hexylresorcinol in the cloudy apple juice. L L -Cysteine was found to be the most significant anti-browning agent. The interaction of kojic acid and 4-hexylresorcinol was found to have a positive effect on the inhibition of enzymatic browning.

- by Alev Bayindirli and +1
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- Food Engineering, Response Surface Methodology, Kojic Acid, Food Sciences

With a deep concern over the probable global food shortage in the years to come, underutilized plant resources are now being extensively tapped by scientists throughout the world. In this regard, sago palm is gaining much importance as a crop par excellence and a starch crop of the 21st century, due to its being an extremely sustainable plant with an ability to thrive in most soil conditions. The review focuses on sago palm as an invaluable resource of starchy foods and of innumerable other products of significant commercial value such as modified starches, lactic acid, cyclodextrins, and ethanol. Several important aspects of the properties and applications of sago palmderived products that could be exploited commercially are also covered.

- by Sajilata Gopalakrishnan
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- Organic Chemistry, SAP, Ethanol, Kojic Acid

Kojic acid, 5-hydroxy-2-hydroxymethyl-γ γ γ γ-pyrone, has many potential industrial applications. In this review, the properties and diverse applications of kojic acid in industries are described. The review also discusses the advance in kojic acid fermentation, focusing on the process development in microorganisms and strain selection, medium and culture optimization, as well as fermentation modes for commercially viable industrial scale production. The performances of various fermentation techniques that have been applied for the production of kojic acid are compared, while the advantages and disadvantages of each technique are discussed in this paper.

- by N Suhaili
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- Biotechnology, Aspergillus, Kojic Acid

Just see to it to utilize the Kojic acid cream and also soap daily, and also if you typically go out imaginable, make sure to make use of some sun block cream for added security. This is to make sure that you could quickly see the... more

- by Ellen Anderson
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- Kojic Acid, Hyperpigmentation, Kojic

In its most basic definition, Skin Lightening products are the use of chemical substances to lighten one's skin tone. From laser treatments to bleaching creams, there are a number of different products and methods that can be used to lighten your skin color. Before you choose a particular product, it is recommended that you first consult your dermatologist to choose a product that will not inadvertently harm your skin. So why do people choose to lighten their skin? Here is a look at the top six reasons why: 1) To Lighten Dark Skin Patches On the Elbows and Underarms-These areas of the skin tend to be darker than the skin on the rest of the body, especially in individuals with light and fair complexions. A high quality skin cream can assist in lightening these patches of skin. 2) To Remove Acne Scars-Those who suffer from acne know that it can be a traumatizing experience. One of the side effects of suffering from acne is that it discolors the skin, and it can make a person feel self-conscious. The proper Skin Lightening cream can reduce the appearance of discoloration. 3) To Reduce the Appearance of Sun Spots-Many people, but especially women, suffer from sunspots or freckles from prior exposure to the sun. Your dermatologist can recommend a natural skin lightener that will assist in reducing their appearance. 4) Even out Your Skin Tone and Brighten Your Complexion-Everyone desires to have bright, healthy and glowing skin. The use of a safe Skin Lightening cream can reveal a brighter complexion and even one's skin tone. A better complexion will increase your self-confidence and give you a reason to smile more often. 5) Affordability-Skin Lightening products, such as creams, are more affordable than traditional laser treatments that are used to lighten skin. Because laser treatments must be performed in a doctor's office, they can be quite expensive, and in most instances, your insurance will not cover their cost. 6) Safety-In the past, women have used homemade products and dangerous skin bleaches to lighten their skin tones. Often times, these bleaching creams contain dangerous ingredients, such as mercury. Therefore, it is important for to choose products that are only recommended by your dermatologist. These are just some reasons a person may choose to use skin-lightening products whether it be a cream or an ointment. The choice is a personal one and any person choosing this route should be sure of their decision before starting the process. Are you looking for more information regarding skin lightening cream Click Here.

- by Skin Glow
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- Nutrition and Dietetics, Pigmentation, Bleaching, Coral Bleaching

To discover safe and effective topical skin-lightening agents, we have evaluated alkyl esters of the natural product gentisic acid (GA), which is related to our lead compound methyl gentisate (MG), and four putative tyrosinase inhibitors, utilizing mammalian melanocyte cell cultures and cell-free extracts. Desirable characteristics include the ability to inhibit melanogenesis in cells (IC 50 Ͻ 100 g/mL) without cytotoxicity, preferably due to tyrosinase inhibition. Of the six esters synthesized, the smaller esters (e.g. methyl and ethyl) were more effective enzyme inhibitors (IC 50 ϳ 11 and 20 g/mL, respectively). For comparison, hydroquinone (HQ), a commercial skin "bleaching" agent, was a less effective enzyme inhibitor (IC 50 ϳ 72 g/mL), and was highly cytotoxic to melanocytes in vitro at concentrations substantially lower than the IC 50 for enzymatic inhibition. Kojic acid was a potent inhibitor of the mammalian enzyme (IC 50 ϳ 6 g/mL), but did not reduce pigmentation in cells. Both arbutin and magnesium ascorbyl phosphate were ineffective in the cell-free and cell-based assays. MG at 100 g/mL exhibited a minimal inhibitory effect on DHICA oxidase (TRP-1) and no effect on DOPAchrome tautomerase (TRP-2), suggesting that MG inhibits melanogenesis primarily via tyrosinase inhibition. MG and GA were non-mutagenic at the hprt locus in V79 Chinese hamster cells, whereas HQ was highly mutagenic and cytotoxic. The properties of MG in vitro, including (1) pigmentation inhibition in melanocytes, (2) tyrosinase inhibition and selectivity, (3) reduced cytotoxicity relative to HQ, and (4) lack of mutagenic potential in mammalian cells, establish MG as a superior candidate skin-lightening agent.

- by Victoria Virador
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- Pigmentation, Enzyme Inhibitors, Cell Culture, Cell line

Kojic acid, 5-hydroxy-2-hydroxymethyl-g-pyrone, has many potential industrial applications. In this review, the properties and diverse applications of kojic acid in industries are described. The review also discusses the advance in kojic acid fermentation, focusing on the process development in microorganisms and strain selection, medium and culture optimization, as well as fermentation modes for commercially viable industrial scale production. The performances of various fermentation techniques
that have been applied for the production of kojic acid are compared, while the advantages and disadvantages of each technique are discussed in this paper.

- by Mohd Shamzi Mohamed
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- Aspergillus, Kojic Acid

Accumulation of the carcinogenic mycotoxin aflatoxin B, has been reported from members of three different groups of Aspergilli (4) Aspergillus flavus, A. flavus var. parvisclerotigenus, A. parasiticus, A. toxicarius, A. nomius, A. pseudotamarii, A. zhaoqingensis, A. bombycis and from the ascomycete genus Petromyces (Aspergillus section Flavi), (2) Emericella astellata and E. venezuelensis from the ascomycete genus Emericella (Aspergillus section Nidulantes) and (3) Aspergillus ochraceoroseus from a new section proposed here: Aspergillus section Ochraceorosei. We here describe a new species, A. rambellii referable to Ochraceorosei, that accumulates very large amounts of sterigmatocystin, 3-O-methylsterigmatocystin and aflatoxin B1, but not any of the other known extrolites produced by members of Aspergillus section Flavi or Nidulantes. G type aflatoxins were only found in some of the species in Aspergillus section Flavi, while the B type aflatoxins are common in all three groups. Based on the cladistic analysis of nucleotide sequences of ITS1 and 2 and 5.8S, it appears that type G aflatoxin producers are paraphyletic and that section Ochraceorosei is a sister group to the sections Flavi, Circumdati and Cervini, with Emericella species being an outgroup to these sister groups. All aflatoxin producing members of section Flavi produce kojic acid and most species, except A. bombycis and A. pseudotamarii, produce aspergillic acid. Species in Flavi, that produce B type aflatoxins, but not G type aflatoxins, often produced cyclopiazonic acid. No strain was found which produce both G type aflatoxins and cyclopiazonic acid. It was confirmed that some strains of A. flavus var. columnaris produce aflatoxin B2, but this extrolite was not detected in the ex type strain of that variety. A. flavus var. parvisclerotigenus is raised to species level based on the specific combination of small sclerotia, profile of extrolites and rDNA sequence differences. A. zhaoqingensis is regarded as a synonym of A. nomius, while A. toxicarius resembles A. parasiticus but differs with at least three base pair differences. At least 10 Aspergillus species can be recognized which are able to biosynthesize aflatoxins, and they are placed in three very different clades.

- by Jens Frisvad
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- Evolutionary Biology, Microbiology, Aspergillus, Phylogeny

Twenty-eight tetraketones (1–28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC50 = 2.06 μM), 11 (IC50 = 2.09 μM), 15 (IC50 = 2.61 μM), and 27 (IC50 = 3.19 μM) were found to be the most active compounds of the series, even better than both standards kojic acid (IC50 = 16.67 μM) and l-mimosine (IC50 = 3.68 μM). This study may lead to the discovery of therapeutically potent agents against clinically very important dermatological disorders including hyperpigmentation as well as skin melanoma.Twenty-eight tetraketones with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors.

- by Ahson Shaikh
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- Organic Chemistry, Enzyme Inhibitors, Kojic Acid, Spectrum analysis

Ficus deltoidea (Mas cotek) water extract has been widely used for woman health in Malaysia. Our investigation focused to identify anti-melanogenic efficacy of F. deltoidea since it has been known to have strong antioxidant activities.... more

- by Young-Kwon Seo
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- Cancer, Archives, Melanin, Dermatology

Direct conversion of gelatinized sago starch into kojic acid byAspergillusflavus strain having amylolytie enzymes was carded out at two different scales of submerged batch fermentation in a 250-mL shake flask and in a 50-L stirred-tank fermentor. For comparison, fermentations were also carried out using glucose and glucose hydrolyzate from enzymic hydrolysis of sago starch as carbon sources. During kojic acid fermentation of starch, starch was first hydrolyzed to glu~ by the action of u-amylase and glucoamylase during active growth phase. The glucose remaining during the production phase (non-growing phase) was then converted to kojic acid. Kojic acid production (23.5 g/L) using 100 g/L sago starch in a shake flask was comparable to fermentation of glucose (31.5 g/L) and glucose hydrolyzate (27.9 g/L) but in the 50-L fermentor was greatly reduced due to non-optimal aeration conditions. Kojic acid production using glucose was higher in the 50-L fermentor than in the shake flask.

- by Mohd. Hassan Mohd. Osman
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- Microbiology, Production, Medical Microbiology, Starch

A total of 11 manganese peroxidase isoenzymes (MnPI-MnPn) with isoelectric points (pIs) in the range of 4.58-3.20 were isolated from liquid-and solid-state cultures of the basidiomycete Ceriporiopsis subvermispora. In the presence of hydrogen peroxide, these isoenzymes showed different requirements for Mn(II) in the oxidation of vanillylacetone, o-dianisidine,p-anisidine and ABTS, whereas oxidation of guaiacol by any isoenzyme did not take place when this metal was omitted. Km values for o-dianisidine and p-anisidine in the absence of Mn(II) are in the range of 0.5-1.0 mM and 4.5-42.0 mM, respectively. Oxalate and citrate, but not tartrate, accelerate the oxidation of o-dianisidine, both in the presence and in the absence of Mn(II).

Fungi are well known for a wealth of pharmacologically important activities and agrochemical properties. Polyketides that are widely found in fungi, are a large group of secondary metabolites which exhibit diversity in their function and structure. Here we described an investigation of three fungal strains which were prospected for production of polyketides. The aim of this work was to employ the diversity of reducing type I polyketide synthase genes in these fungi using a molecular and bioinformatics approaches as a mini tool. A degenerate primer pair for highly reduced PKSs was newly designed and used together with ketosynthase primers for amplification. One hundred and thirty-eight clones were sequenced. Ten KS domain sequences were isolated, using two primer pairs specific for highly reduced type PKSs. This study revealed four sequences from Emarcea castanopsidicola, four ketosynthase sequences from Gaeumannomyces amomi and two sequences from Leiosphaerella amomi, respectively. Bioinformatic techniques were employed to identify a group of these KS domain sequences. Based on these sequences suggested that rapid screening provided the potential to explore significant PKS structural diversity. Hence chemical investigation had been conducted and exhibited nine compounds. The endophytic fungus L. amomi was cultivated and elucidated linoleic acid, ergosterol and an unidentified sterol in the extracts. Linoleic acid, sitosterol, and p-hydroxybenzoic acid were isolated from the saprobic fungus E. castanopsidicola. We first isolated a new polyketide, stemphol 1-O-β-D-galactopyranoside together with four known metabolites; stemphol, kojic acid, ergosterol, indole-3-carboxylic acid from an ethyl acetate extract of the cultures of G. amomi. Stemphol was classified as a phenolic lipid or resorcinolic lipid, which have biopharmacological, biomedical, and biotechnological importance. However, recent researches have revealed that these molecule types are synthesized by 2′-oxoalkylresorcinolic acid synthase. The prospective KS domain sequences from this study will be used as probes to isolate putative PKS genes. A gene cluster responsible for PK biosynthesis should be confirmed by determination of PK products generated by these enzymes.

- by juangjun jumpathong and +1
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- Technology, Biological Sciences, Kojic Acid, Secondary Metabolites

To explore the biotechnological potential of endophytic fungi for kojic acid production by static and submerged cultivation. Two hundred and fourteen endophytic fungal isolates collected from apparently healthy leaves of eleven common medicinal plants in Egypt were screened for production of the acid using static cultivation at 28 °C and all positive isolates were examined for their production using submerged technique at 220 rpm. Twenty four endophytic fungal isolates showed the ability to produce kojic acid; these isolates belong to Aspergillus (five isolates of two species and two species varieties), Petromyces (nine isolates of two species), Penicillium (six isolates of four species), Chaetomium globosum (two isolates) and one isolate from each of Emericella nidulans and Pleospora allii. Production levels of kojic acid by static cultures fluctuated between 0.89 ± 0.05 and 23.84 ± 0.1 g/L. On the other side, Kojic acid production levels using submerged technique at 220 rpm fluctuated between 1.34 ± 0.28 and 36.75 ± 1.91 g/L. Maximum production level of kojic acid using submerged cultivation was exhibited by Petromyces flavus No. 64 (36.75 ± 1.91 g/L) isolated from Datura stramonium followed by Aspergillus flavus var. columnaris No. 69 (35.41 ± 0.5 g/L) isolated from Rosmarinus officinalis.

- by Orkida Monir
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- Microbiology, Biotechnology, Biology, Fungal endophytes

Tyrosinase is the key enzyme in melanin synthesis, and kojic acid is a widely available inhibitor against tyrosinase with extensive application values. The inhibitory mechanism of kojic acid was elaborated by studying the mutual... more

- by Sift Desk Journals
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- Kojic Acid, Tyrosinase

Introduction: Although pain is traditionally considered to be mediated by neurons, recent research has shown the important roles of glial cells in pain sensation. Microglial cells have been implicated in such processes, but less is known about the role of astrocytes. Astrogliosis is recognized as a defence reaction, conceivably aimed at limiting tissue damage and restoring homeostasis. This study aimed to assess the expression of glial fibrillary acidic protein (GFAP) in astrocytes from the frontal cortex, hypothalamus and periaqueductal grey matter (PAG) after administration of short-term doses of distinct drugs used for pain management, but without painful stimuli. Materials and Methods: Male Wistar rats received amitriptyline (Amt, 10 mg/kg/day) or gabapentin (Gb, 60 mg/kg/day) for 10 days, by gavage or via the intraperitoneal route, methadone (Me, 4.5 mg/kg/day), morphine (Mo, 10 mg/kg/day), carbamazepine (Cbz, 40 mg/kg/day), fluoxetine (Flx, 10 mg/kg/day), amantadine (Ama, 10 mg/kg/day), S-ketamine (Ke, 50 mg/kg/day), dipyrone (Dip, 16 mg/kg/day) or 0.9% saline solution (daily). Brain samples were collected for GFAP immunohistochemical investigation in the frontal cortex, hypothalamus and PAG. Results: Morphometric analysis showed that all drugs increased GFAP expression and astrocyte size in the frontal cortex and hypothalamus in relation to the saline group. In the PAG this expression was increased in the groups treated with Amt, Me, Mo, Ama, Flx and Ke, but not with Gb, Cbz and Dip. Discussion: Although the precise meaning of such changes remains unclear, astrocytes appeared to react phenotypically to distinct classes of pain modulators in almost all investigated areas, probably influencing neurons and the entire neural microenvironment.

- by T-L Mandalian
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- Pathology, Ichthyology, Veterinary Pathology, Environmental Toxicology

Machine learning is a branch of artificial intelligence that allows computer systems to learn directly from examples, data, and experience. Statistical modeling is more about finding connections between variables and consequently the impact of these relationships, whilst also catering for prediction. It should be clear that these two methodologies are dissimilar in their objective, despite using alike means to arrive there. The valuation of the machine learning algorithm uses a test set to validate its accuracy. Though, for a statistical model, analysis of the regression parameters via confidence intervals, significance tests, and other tests can be used to evaluate the model’s legitimacy. To demonstrate the applications and utility of this theory, we performed an experimental study on zebrafish exposed to the mycotoxin. Methods: Patulin (70 µg/L) and kojic acid (100 mg/L, 204 mg/L, and 284 mg/L) were administered by immersion to zebrafish once daily for 7 days period before the behavior testing. The following behavioral tests were performed: Novel Tank test (NTT) (to assess the explorative behavior and anxiety); Y Maze test (which measures the spontaneous explorative behavior). Behavioral tests were performed on separate days. For the behavior tests, the statistical analysis was performed using ANOVA variation analysis (two-way ANOVA). All results are expressed as the mean ± standard error of the mean. The values of the general index F for which p <0.05 were considered statistically significant. Results: Y-maze - Patulin exposure led to an intensification of the locomotor activity, an increased traveled distance and number of arm entries. By increasing the spontaneous alternation between the aquarium’s arms, Patulin has shown a stimulating effect on spatial memory. In the case of zebrafish exposed to 100 mg /l kojic acid, the traveled distance was shorter by 27% than the distance attained by those in the control group. The higher doses of kojic acid (204 mg / l and 284 mg / l) lead to an increased locomotor activity, distance traveled, number of arm entries and the spontaneous alternation. The increase in spontaneous alternation demonstrates that 204 mg/l and 284 mg/l kojic acid doses had a stimulating effect on spatial memory. Novel Tank test - Compared to the control group, the traveled distance of the patulin exposed fish is slightly reduced. Compared to the control group, the traveled distance of the kojic acid exposed fish is reduced, due to a shorter mobile time (by 25-27% in the case of fish exposed to 204 mg / L and 284 mg / L kojic acid). Patulin and kojic acid exhibits toxic effects on zebrafish liver, kidney, myocardium and leads to severe alteration. We continued the analysis trying some machine learning algorithms on the classification problems in the case of the two behavioral tests MAZE and NTT, after which we concluded that the results were better in the case of the NTT test relative to the MAZE test and that the use of decision tree algorithms leads to amazing results, knowing that their hierarchical structure allows them to learn signals from both classes. Conclusions: The groups exposed to patulin and kojic acid show histological changes in the liver, kidneys, and myocardial muscle tissue. The novel tank test, which assesses the explorative behavior, proved to be conclusive in the behavioral analysis of fish that were given toxins, proving that intoxicated fish had a decreased explorative behavior and an increased anxiety. We have managed to detect an automatic learning algorithm, from the category of decision trees, which can be trained to classify the behavior of fish that were administered a toxin from the category of those used in the experiment, only by analyzing the characteristic features of the NTT behavioral test.

- by T-L Mandalian and +2
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- Statistics, Machine Learning, Toxicology, Statistical Analysis
- by Bruno Kubata
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- Engineering, Technology, Production, Experimental Design

In the present paper, tyrosinase inhibition studies and structure–activity relationship of eight cycloartane glycosides and one cucurbitane glycoside and its genin, which were isolated from Astragalus (Leguminoseae) and Bryonia (Cucurbitaceae) plants, have been discussed. The activities are compared with two reference tyrosinase inhibitors, kojic acid and l-mimosine. These studies and the SAR showed that the askendoside B which exhibited highly potent (IC50 = 13.95 μM) tyrosinase inhibition could be a possible lead molecule for the development of new medications of several skin diseases related with the over-expression of the enzyme tyrosinase, like hyperpigmentation. The molecule also may be interesting for the cosmetic industries as a skin whitening agent.

- by IQBAL HASSAN
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- Organic Chemistry, Kojic Acid, Peptides, Enzyme
- by Mohd. Hassan Mohd. Osman
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- Engineering, Technology, Bioscience, Biological Sciences

To aid the pharmaceutical and cosmetic industry in the development of alternatives to prevent melaninrelated hyperpigmentation disorders, the plant Dalea elegans was submitted to fractionation with the aim of obtaining its anti-tyrosinase principle. Bioguided fractionation of D. elegans led to the isolation of 5,2 0 ,4 0 -trihydroxy-2 00 ,2 00 -dimethylchromene-(6,7:5 00 ,6 00 )-flavanone (1) as the active compound. This novel flavanone, named as dalenin, showed notable activity at inhibiting tyrosinase using L-tyrosine or L-DOPA as substrates with IC 50 values of 0.26 and 18.61 lM, respectively. This meant that the flavanone was 52 and 495 times more effective as a monophenolase inhibitor than hydroquinone and kojic acid, respectively. With L-DOPA as a substrate, compound 1 showed itself 59 times more effective at inhibiting the enzyme than hydroquinone and showed the same level of effectiveness as that of kojic acid. It was found that the flavanone behaved as a reversible inhibitor of the enzyme and that it was a mixed-I type or a non-competitive inhibitor with L-tyrosine or L-DOPA as substrates, respectively. Molecular modeling studies were conducted confirming the inhibitory potency of dalenin and showing that the 2 0 ,4 0 -dihydroxy substituents are important for the interaction with the enzyme.

- by Sara Palacios
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- Organic Chemistry, Kinetics, Modeling, Enzyme Inhibitors

- by Corina Ursulescu
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- Statistics, Machine Learning, Toxicology, Statistical Analysis

Ramalin (␥-glutamyl-N -(2-hydroxyphenyl)hydrazide), a novel compound, was isolated from the methanol-water extract of the Antarctic lichen Ramalina terebrata by several chromatographic methods. The molecular structure of ramalin was determined by spectroscopic analysis. The experimental data showed that ramalin was five times more potent than commercial butylated hydroxyanisole (BHA) in scavenging 1-diphenyl-2-picryl-hydazil (DPPH) free radicals, 27 times more potent in scavenging 2,2 -azino-bis (3-ethylbenzthiazoline-6-sulfonic acid free radicals (ABTS • + ) than the vitamin E analogue, trolox, and 2.5 times more potent than BHT in reducing Fe 3+ to Fe 2+ ions. Similarly, ramalin was 1.2 times more potent than ascorbic acid in scavenging superoxide radicals and 1.25 times more potent than commercial kojic acid in inhibiting tyrosinase enzyme activity, which ultimately leads to whitening of skin cells. Ramalin showed no or very little cytotoxicity in human keratinocyte and fibroblast cells at its antioxidant concentration. Furthermore, ramalin was assessed to determine its antioxidant activity in vivo. One microgram per milliliter ramalin significantly reduced the released nitric oxide (NO) and 0.125 g/ml ramalin reduced the produced hydrogen peroxide (H 2 O 2 ) in LPS (lipopolysaccharide)stimulated murine macrophage Raw264.7 cells. Considering all the data together, ramalin can be a strong therapeutic candidate for controlling oxidative stress in cells.

- by Se Jong Han
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- Free Radicals, Complementary and Alternative Medicine, Plant Biology, Free Radical

Aspergillus oryzae NRRL 35191 was isolated as an endophyte from coffee leaves and found to produce kojic acid (KA) in culture. When inoculated into cacao seedlings (Theobroma cacao), A. oryzae grew endophytically and synthesized KA in planta. Cacao seedlings inoculated with A. oryzae produced higher levels of caffeine than noninoculated ones. Aspergillus oryzae may be a useful endophyte to introduce to cacao since it grows nonpathogenically and induces the caffeine defense response that may make the plant more tolerant to insects and pathogens.

- by Fábio Chaves
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- Microbiology, Kojic Acid, Theobroma Cacao

Optimization of process conditions to achieve maximum yield of kojic acid was carried out with a soil isolated fungal culture Aspergillus flavus. Five physicochemical factors which significantly influence the production were screened using a non-statistical One-factor-at-a-time method (OFAT) and later statistical Central Composite Design (CCD) and Response surface methodology (RSM) were performed for designing of the experiment, analysis of results to study the interaction among the parameters. The maximum production of 82.6g/L of kojic acid was noticed at optimized conditions of Carbon source concentration i.e., starch hydrolysate of Sago starch 100ml, Peptone concentration 4g/L, KH2PO4 concentration 1g/L, MgSO4 concentration 0.5g/L, pH 6.0, Time 28d and Temperature 280C with OFAT method whereas the production yield was enhanced significantly to 90.8g/L with response surface methodology. It was estimated from the model that the determination co-efficient was (R2=0.9561) represented that 95.61% of the variability in the response could be interpreted by the model and the results showed an excellent adequacy of the multiple-regression model. During the last phase of the kojic acid fermentation, the entire fermented broth was subjected to evaporation followed by crystallization and the purity of the crystal was confirmed by X-ray crystallography.

Kojic acid is a fungal metabolite commonly produced by many species of Aspergillus, Acetobacter, and Penicillium. The Aspergillus flavus group has tradiationally been used in the production of a number of foods, including miso (soybean paste), shoyu (soy sauce), and sake. Kojic acid is widely used as a food additive for preventing enzymatic browning, and in cosmetic preparations as a skin-lightening or bleaching agent. Because kojic acid is often produced during the fermentation of historically used dietary staples, it has a long history of consumption. Various types of compounds, such as glucose, sucrose, acetate, ethanol, arabinose, and xylose, have been used as carbon sources for kojic acid production. Different Aspergillus species are known to produce variable amounts of kojic acid. The mechanism of action of kojic acid is well defined and it has been shown to act as a competitive and reversible inhibitor of animal and plant polyphenol oxidases, xanthine oxidase, and D-and some L-amino acid oxidases. The structure of kojic acid indicates a relatively simple route of metabolism much like dietary hexoses. Acute or subchronic toxicity resulting from an oral dose has not been reported, but convulsions may occur if kojic acid is injected. Results of mutagenicity studies are mixed, but in the in vivo mammalian dominant lethal assay, kojic acid was proven negative. Continuous administration of high doses of kojic acid in mice resulted in induction of thyroid adenomas in both sexes. Kojic acid reversibly affects thyroid function primarily by inhibiting iodine uptake, leading to decreases in T 3 and T 4 and increase in TSH. Increased TSH from pituitary gland in turn stimulates thyroid hyperplasia. Several lines of evidence indicate that the proliferative effects of kojic acid on thyroid are not related to a genotoxic pathway. The risk of functional inhibition of iodine uptake and its metabolism (organification) and thyroid tumor induction by kojic acid in humans appears to be extremely low. Based on the literature reviewed and discussed here, consumption of kojic acid at levels normally found in food does not present a concern for safety.

- by George Burdock
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- Chemistry, Metabolism, Medicine, Literature Review
- by Bruno Kubata
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- Engineering, Technology, Production, Experimental Design

Kojic acid exhibited a competitive inhibition for the oxidation of chlorogenic acid and catechol by potato polyphenol oxidase (PPO) and of 4-methylcatechol and chlorogenic acid by apple PPO. This compound showed a mixed-type inhibition for white shrimp, grass prawn, and lobster PPO when DL-0-3,4-dihydroxyphenylalanine (DL-Dopa) and catechol were used as substrates but a mixed-type and a competitive inhibition for mushroom PPO when DL-Dopa and L-tyrosine were used, respectively. Potato and apple PPOs were shown to have much higher affinities for Dopa than for chlorogenic acid, 4-methylcatechol, and catechol. These two PPOs also had a higher affinity for Dopa than the other four PPOs. Kojic acid is thus an effective inhibitor of PPO on the oxidation of Dopa.

- by Rosa Rolle
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- Engineering, Kinetics, Kojic Acid, Agricultural

The tyrosinase inhibitory potential of seventeen synthesized oxazolone derivatives has been evaluated and their structure–activity relationships developed in the present work. All the synthesized derivatives, 3–19, demonstrated excellent in vitro tyrosinase inhibitory properties having IC50 values in the range of 1.23 ± 0.37–17.73 ± 2.69 μM, whereas standard inhibitors l-mimosine and kojic acid have IC50 values 3.68 ± 0.02 and 16.67 ± 0.52 μM,, respectively. Compounds 4–8 having IC50 values 3.11 ± 0.95, 3.51 ± 0.25, 3.23 ± 0.66, 1.23 ± 0.37, and 2.15 ± 0.75, respectively, were found to be very active members of the series, even better than both the standard inhibitors. However, compounds 3, 9–11, 13, 14, 16, 17, and 19 were found to be better than kojic acid but not l-mimosine. (2-Methyl-4-[E,2Z)-3-phenyl-2-propenyliden]-1,3-oxazol-5(4H)-one (7) bearing a cinnamyol residue at C-4 of oxazolone moiety and an IC50 = 1.23 ± 0.37 μM was found to be the most active one among all tested compounds. These studies reveal that the substitution of functional group (s) at C-4 and C-2 positions plays a vital role in the activity of this series of compounds. It is concluded that compound 7 may act as a potential lead molecule to develop new drugs for the treatment of tyrosinase based disorders.Seventeen oxazolone derivatives were synthesized, characterized, and screened for tyrosinase inhibition.

- by IQBAL HASSAN
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- Organic Chemistry, Kojic Acid, Peptides, Levodopa

A scaled-up isolation and purification procedure is described for tyrosinase from Streptomyces antibioticus. Kinetic Ž . studies of the enzyme catalysed conversion of L-3,4-dihydroxyphenylalanine L-DOPA into DOPAchrome show that kojic acid, L-mimosine, p-toluic acid and benzoic acid exhibit competitive inhibition with inhibition constants of 3.4, 30, 1.9 = 10 2 and 8.0 = 10 2 mM, respectively. Paramagnetic NMR techniques appear well suited to study the binding of inhibitors to the active site. From the variation of the NMR shifts with temperature a value of y2 J s 156 " 6 cm y1 is Ž . derived for the exchange coupling between the unpaired spins on the two Cu II ions in the active site of the met-tyrosinaserkojic acid complex. q

- by Gerard Canters and +1
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- Kinetics, Copper, Kojic Acid, Scaling up
- by Bruno Kilunga Kubata
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- Engineering, Technology, Production, Experimental Design

This paper reports the effect of the tyrosinase (monophenol o-diphenol:oxygen oxidoreductase; EC 1.14.18.1) inhibitors diethyldithiocarbamate (DETC), L-tropolone, kojic acid, phenylthiourea (PTU) and L-mimosine on the in vitro growth of Tuber borchii (a white truffle) mycelium. A significant inhibitory effect on mycelium growth was observed for DETC, PTU and L-tropolone (0% growth compared to control at 100 μg ml−1 DETC, PTU and L-tropolone and at 10 μg ml−1 DETC and L-tropolone). As a comparison the action of the same inhibitors was also tested on the growth and pigmentation of the mould Cladosporium sphaerospermum. In the presence of CuSO4 10−6 M T. borchii mycelium acquired pigmentation (as rounded aggregates compared to control revealed by SEM microscopy). Tyrosinase activity in the extract from T. borchii mycelium (18-day culture) was detected spectrophotometrically.

- by Giovanni Pacioni
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- Scanning Electron Microscopy, Enzyme Inhibitors, Biological Sciences, Mycotoxins

In our efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian plants belonging to 24 families for tyrosinase inhibitory activity. The extracts of 5 Artocarpus woods showed potent tyrosinase inhibitory activity (over 80% at 100 µg/ml) similar to a positive control, kojic acid. In Artocarpus woods, the extracts of the sapwoods showed stronger inhibitory activity than those of the heartwoods. Chlorophorin was isolated as one of the active compounds in the sapwood of Artocarpus heterophyllus. The content of chlorophorin in sapwood was higher than that in heartwood.

- by Enos Tangke Arung
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- Wood Science, Wood, Kojic Acid, Forestry Sciences

In the present paper, tyrosinase inhibition studies and structure-activity relationship of eight cycloartane glycosides and one cucurbitane glycoside and its genin, which were isolated from Astragalus (Leguminoseae) and Bryonia (Cucurbitaceae) plants, have been discussed. The activities are compared with two reference tyrosinase inhibitors, kojic acid and L L-mimosine.

- by Muhammad Reyhan
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- Organic Chemistry, Kojic Acid, Peptides, Enzyme

The immobilization of tyrosinase onto glutaraldehyde activated streptavidine magnetic particles and subsequent retention onto a magnetized carbon paste electrode for the amperometric assay of tyrosinase inhibitors is described. Tyrosine was used as substrate as it is the first substrate in the melanogenesis process. The sensing mode is based on monitoring the decrease of the amperometric signal corresponding to the electrochemical reduction of dopaquinone enzymatically generated. This current decrease is due to the presence of inhibitors acting directly on the enzyme or inhibitors acting on the product of the enzymatic reaction, i.e. dopaquinone. The methodology is designed for the evaluation of the inhibitory potency of the most frequently used active substances in cosmetic marketed products against hyperpigmentation such as kojic acid, azelaic acid and benzoic acid. These compounds bind to the tyrosinase active center. Ascorbic acid is also investigated as it interrupts the synthesis pathway of melanin by reducing the melanin intermediate dopaquinone back to l-dopa. By comparing the obtained IC 50 , under the same experimental conditions, the order of their inhibitory potency was: kojic acid (IC 50 = 3.7 × 10 −6 M, K i = 8.6 × 10 −7 M), ascorbic acid (IC 50 = 1.2 × 10 −5 M), benzoic acid (IC 50 = 7.2 × 10 −5 M, K i = 2.0 × 10 −5 M) and azelaic acid (IC 50 = 1.3 × 10 −4 M, K i = 4.2 × 10 −5 M) in close agreement with literature spectrophotometric inhibition data using the soluble tyrosinase.

- by Stéphanie Patris
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- Analytical Chemistry, Electrochemistry, Kinetics, Enzyme Inhibitors

- by Alin Vasilescu
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- Artificial Intelligence, Statistics, Machine Learning, Toxicology

Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having... more

Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4H-pyran-4-one structure (compounds 1-30) with inhibitory effects on tyrosinase enzyme were described. One-pot Mannich reaction was carried out by using kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in presence of formaline. Subsequently, cyclic amine (morpholine, piperidine and pyrrolidine) derivatives of the 6th-position of chlorokojic acid were obtained with nucleophilic substitutions in basic medium. The structures of new compounds were identified by FT-IR, 1H- and 13C NMR, ESI-MS and elemental analysis data. The potential mushroom tyrosinase inhibitory activity of the compounds were evaluated by the spectrophotometric method using l-DOPA as a substrate and kojic acid as the control agent. The potential inhibitory activity was also investigated in silico using molecular docking simulation method. Tyrosinase inhibitory action was significantly more efficacious for several compounds (IC50: 86.2-362.1 µM) than kojic acid (IC50: 418.2). Compound 3 bearing 3,4-dichlorobenzyl piperazine moiety was proven to have the highest inhibitory activity. The results of docking studies showed that according to the predicted conformation of compound 3 in the enzyme binding site, hydroxymethyl group provides a metal complex with copper ions and enzyme. Thus, this interaction explain the high inhibitory activities of the compounds 1, 3 and 4 possessing hydroxymethyl substituent supporting the mushroom assay results with docking studies. In accordance with the results, it is suggested that Mannich bases of kojic acid bearing substituted benzyl piperazine groups (compounds 1, 3, 4, 11, 13, 14, 23, 24, 28, and 29) could be promising antityrosinase agents. Additionally, considering the relationship between tyrosinase inhibitory activity results and molecular docking, a new tyrosinase inhibition mechanism can be proposed.

- by Gülşah Karakaya
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- Organic Chemistry, Bioorganic Chemistry, Kojic Acid, Mannich base

After testing several chromatographic systems described in the literature, the optimal operating conditions were retained to develop a simple and rapid method grouping TLC and HPLC/UV for separation, identification and dosage of kojic acid (CAS RN 501-30-4) or arbutine (CAS RN 497-76-7) in skin-whitening cosmetic products. The screening is carried out by TLC on cellulose plate and by TLC on silicagel plate with UV indicator and polar mobile solvent. Regarding identification and quantitative determination by HPLC/UV, the best results were obtained by direct phase chromatography, using a polar stationary phase greffed with diol groups and a polar buffered mobile phase at PH 2,5. Intralaboratory prevalidation tests were carried out on the HPLC method: detection limit, linearity and intralaboratory repeatability of standard curves and repeatability of samples quantitative determination.

- by Leo Goeyens
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- Chemistry, Medicine, Quantitative analysis, Kojic Acid

Two natural products Polypodium leucotomos extract (PL) and kojic acid (KA) were tested for their ability to scavenge reactive oxygen species (• OH, • O 2-, H 2 O 2 , 1 O 2) in phosphate buffer. Hydroxyl radicals were generated by the Fenton reaction, and the rate constants of scavenging were 1.6 x 10 9 M-1 s-1 for KA and 1.0 x 10 9 M-1 s-1 for PL, similar to that of ethanol (1.4 x 10 9 M-1 s-1). With superoxide anions generated by the xanthine/hypoxanthine system, KA and PL (0.2-1.0 mg/ml) inhibited • O 2-dependent reduction of nitroblue tetrazolium by up to 30 and 31%, respectively. In the detection of 1 O 2 by rose bengal irradiation, PL at 1.0 mg/ml quenched singlet oxygen by 43% relative to azide and KA by 36%. The present study demonstrates that PL showed an antioxidant effect, scavenging three of four reactive oxygen species tested here. Unlike KA, PL did not significantly scavenge hydrogen peroxide.

- by Antonio Tedesco
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- Chemistry, Medicine, Antioxidants, Reactive Oxygen Species

The tyrosinase inhibitory potential of seventeen synthesized oxazolone derivatives has been evaluated and their structureactivity relationships developed in the present work. All the synthesized derivatives, 3-19, demonstrated excellent in vitro tyrosinase inhibitory properties having IC 50 values in the range of 1.23 ± 0.37-17.73 ± 2.69 lM, whereas standard inhibitors L L-mimosine and kojic acid have IC 50 values 3.68 ± 0.02 and 16.67 ± 0.52 lM,, respectively. Compounds 4-8 having IC 50 values 3.11 ± 0.95, 3.51 ± 0.25, 3.23 ± 0.66, 1.23 ± 0.37, and 2.15 ± 0.75, respectively, were found to be very active members of the series, even better than both the standard inhibitors. However, compounds 3, 9-11, 13, 14, 16, 17, and 19 were found to be better than kojic acid but not L L-mimosine. (2-Methyl-4-[E,2Z)-3-phenyl-2-propenyliden]-1,3-oxazol-5(4H)-one (7) bearing a cinnamyol residue at C-4 of oxazolone moiety and an IC 50 = 1.23 ± 0.37 lM was found to be the most active one among all tested compounds. These studies reveal that the substitution of functional group (s) at C-4 and C-2 positions plays a vital role in the activity of this series of compounds. It is concluded that compound 7 may act as a potential lead molecule to develop new drugs for the treatment of tyrosinase based disorders.

- by Shahnaz Perveen
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- Organic Chemistry, Kojic Acid, Peptides, Levodopa

Heliothis virescens larval plasma contains high levels of an antiviral activity against the budded form of the Helicoverpa zea single nucleopolyhedrovirus (HzSNPV) in vitro. Preliminary results indicated that phenoloxidase is primarily responsible for this virucidal effect. However it is known that other enzymes that generate antimicrobial reactive oxygen intermediates and reactive nitrogen intermediates are present in hemolymph that could contribute to the observed virucidal activity. To elucidate the contributions of phenoloxidase and other candidate activities to plasma innate immune response against baculovirus infection specific metabolic inhibitors were used. In vitro the general inhibitors of melanization (N-acetyl cysteine, ascorbate and glutathione), and specific inhibitors of phenoloxidase (phenylthiourea and Kojic acid), completely blocked virucidal activity up to the level seen in controls. Addition of the enzyme superoxide dismutase to plasma did not affect virucidal activity; however addition of catalase had an inhibitory effect. Inhibitors of nitric oxide synthase activity did not affect virucidal activity. Our results confirm that phenoloxidase is the predominate activity in larval plasma accounting for inactivation of HzSNPV in vitro, and that phenoloxidase-dependent H 2 O 2 production may contribute to this virucidal activity.

- by Holly Popham
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- Zoology, Tobacco, Glutathione, Catalase

QSAR (quantitative structure–activity relationship) studies of tyrosinase inhibitors employing Dragon descriptors and linear discriminant analysis (LDA) are presented here. A data set of 653 compounds, 245 with tyrosinase inhibitory activity and 408 having other clinical uses were used. The active data set was processed by k-means cluster analysis in order to design training and prediction series. Seven LDA-based QSAR models were obtained. The discriminant functions applied showed a globally good classification of 99.79% for the best model Class=−96.067+1.988×210X0Av+91.907BIC3+6.853CIC1Class=−96.067+1.988×102X0Av+91.907BIC3+6.853CIC1 in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. This external prediction set had an accuracy of 99.44%. After that, the developed models were used in ligand-based virtual screening of tyrosinase inhibitors from the literature and never considered in either training or predicting series. In this case, all screened chemicals were correctly classified by the LDA-based QSAR models. As a final point, these fitted models were used in the screening of new bipiperidine series as new tyrosinase inhibitors. These methods are an adequate alternative to the process of selection/identification of new bioactive compounds. The biosilico assays and in vitro results of inhibitory activity on mushroom tyrosinase showed good correspondence. It is important to stand out that compound BP4 (IC50 = 1.72 μM) showed higher activity in the inhibition against the enzyme than reference compound kojic acid (IC50 = 16.67 μM) and l-mimosine (IC50 = 3.68 μM). These results support the role of biosilico algorithm for the identification of new tyrosinase inhibitor compounds.

- by Gerardo M Casanola-Martin and +1
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- Organic Chemistry, Computational Biology, Chemometrics, Prediction
- by Seon-Yeong Kwak
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- Peptide Science, Enzyme Inhibitors, Stability, Biological Sciences

A series of water soluble compounds of general formula [{(η 6 -arene)Ru(HMP)Cl], [η 6arene = η 6 -cymene (1), η 6 -HMB (2), η 6 -C 6 H 6 (3); HMP = 5-hydroxy-2-(hydroxymethyl)-4-pyrone] have been prepared by the reaction of [{(η 6 -arene) RuCl 2 } 2 ] with HMP. The complexes 1 and 2 react with NaN 3 to give in excellent yield tetra-azido complexes [{(η 6 -arene)Ru(μN 3 )N 3 } 2 ] (arene = cymene 4, HMB = 5) but similar reaction of complex 3 with NaN 3 yielded di-azdo complex [{(η 6 -C 6 H 6 )Ru(μN 3 )Cl} 2 ] (6). Reaction of [{(η 6 -arene)Ru(μN 3 )Cl} 2 ] with HMP in the presence of NaOMe resulted in the formation of azido complex [{(η 6 -arene)Ru(HMP)N 3 ]. Mono and dinuclear complexes [{(η 6 -arene)Ru(HMP)(L 1 )] + and [{(η 6 -arene)Ru(HMP)} 2 (μL 2 )] 2+ were also prepared by the reaction of complexes 1 and 2 with the appropriate ligand, L 1 or L 2 in the presence of AgBF 4 (L 1 = PyCN, DMAP; L 2 = 4,4'bipy, pyrazine). The complexes are characterized on the basis of spectroscopic data and molecular structures of three representative compounds have been determined by single crystal X-ray diffraction study.

- by Keisham Sarjit
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- Inorganic Chemistry, Crystallography, Kojic Acid, X ray diffraction