Daniela Ilieva Batovska | Bulgarian Academy of Sciences (original) (raw)

Papers by Daniela Ilieva Batovska

ABSTRACT By original sonochemical modification of Wittig reaction 21 cholesteryl esters of cinnam... more ABSTRACT By original sonochemical modification of Wittig reaction 21 cholesteryl esters of cinnamic acid derivatives are synthesised. Two of the synthesised esters manifest a marked activity against PV1 and another seven compounds show a borderline effect towards the same virus. In some cases a structure-activity connection has been determined. The measurements of the radical scavenging efficiency of cholesteryl esters of caffeic, o-, m- and p-coumaric acids by a chemiluminescence method characterise them as good inhibitors of liquid phase oxidation of tetraline at 353 K. It is demonstrated that the double bond of the cholesteryl moiety has an insignificant effect on antioxidant activity. New amides of cinnamic acid derivatives with 3α- and 3β- cholestanylamines, as well as with α- and β-N-(2′-aminoethyl)- 3-aminocholest-5-en were synthesised using dicyclohexylcarbodiimide (DCC) and 1-hydroxy-benzotriazole as efficient additives. Their antibacterial activity against Staphylococcus aureus was investigated.

Journal of Intercultural Ethnopharmacology, 2015

Bulgarian Journal of Agricultural Science

Methanolic extracts from the aerial and root parts of in vitro cultured Artemisia alba and the ae... more Methanolic extracts from the aerial and root parts of in vitro cultured Artemisia alba and the aerials of in vitro cultured Clinopodium vulgare, Hypericum tetrapterum,H. richeri and the endemic H. rumeliacum were evaluated for their nitric oxide scavenging capacities. Extracts of H. rumeliacum, H. richeri and H. tetrapterum exhibited remarkably higher activity (0.18, 0.17 and 0.97 mg.ml–1 , respectively) compared to C. vulgare and A. alba (SC50 = 3.45, 2.93 and 2.62 mg.ml–1, respectively). Vitamin C (a reference compound), exhibited activity of 0.26 mg.ml–1. The presented results are indicative of the high therapeutic potential of the extracts derived from the in vitro cultured plants and are a good basis for further more detailed research

In vivo (Athens, Greece)

The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport... more The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in...

Molecules (Basel, Switzerland), 2005

Natural monoglycerides of cinnamic, ferulic and p-coumaric acids were synthesized in good to high... more Natural monoglycerides of cinnamic, ferulic and p-coumaric acids were synthesized in good to high overall yields from isopropylidene glycerol via the Mitsunobu reaction and further deprotection of the corresponding acetonides with Amberlyst 15. The method avoids the need of protection of the phenolic hydroxyls. During the Mitsunobu esterifications a strong influence of the acid strength on the efficacy and outcome of the reaction was observed.

Molecules, 2005

Journal of the Serbian Chemical Society, 2009

The leaf surface is the first barrier of grapevine plants towards various environmental stressors... more The leaf surface is the first barrier of grapevine plants towards various environmental stressors causing damage in vineyards. For this reason, identification of leaf surface metabolites in grapevine and their putative role in plant-environment interactions is important for viticulture. In this study, the leaf surface components of 16 grapevine plants (Vitis vinifera) growing in an experimental vineyard were analyzed in two consecutive seasons -the summer and the autumn of 2007. Forty-eight individual metabolites typical of the cuticular plant wax were identified by gas chromatography-mass spectrometry (GC--MS). They belonged to the following groups of compounds: hydrocarbons, sterols, terpenes, free and esterified fatty acids, alcohols, aldehydes and ketones. The metabolic profiles of the summer and the autumn samples were statistically different (P < 0.05), which was mainly attributed to the specific insects present in the two seasons and to the adaptation of the grapevine to lower temperatures.

International Journal of Medicinal Chemistry, 2011

ABSTRACT Based on the structure of three previously established lead compounds, fifteen selected ... more ABSTRACT Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4 μg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers.

Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish Society of Microbiologists, 2009

The antibacterial activity of the medium chain fatty acids and their 1-monoglycerides was evaluat... more The antibacterial activity of the medium chain fatty acids and their 1-monoglycerides was evaluated towards several Gram-positive strains belonging to the genera Staphylococcus, Corynebacterium, Bacillus, Listeria and Streptococcus. The 1-monoglycerides were more active than the fatty acids with monolaurin being the most active compound. Interesting effects were observed when the streptococcal strain Streptococcus pyogenes was used as a test microorganism. First, blocking of the hydroxyl groups of the glycerol moiety of monolaurin led to a compound with remarkable antibacterial activity (MIC, 3.9 microg/ml). Secondly, synergistic relationships were observed between monolaurin and monocaprin as well as between monolaurin and the poorly active lauric acid when their two component mixtures were examined. The mixtures in which one of the components was 2-fold more predominant than the other one were much more active than the pure components taken individually. Moreover, the presence of ...

Journal of Bioscience and Bioengineering, 2005

Efficient selective synthesis of the secondary amide surfactant N-methyl lauroylethanolamide from... more Efficient selective synthesis of the secondary amide surfactant N-methyl lauroylethanolamide from methyl laurate and N-methylethanol amine by carrier-fixed Chirazyme L-2 (Candida antarctica) using a kinetic strategy has been demonstrated. When different solvents were screened for product yields using Chirazyme L-2, acetonitrile was found to be optimal. The rate of the reaction increased sharply by increasing the molar ratio of the reactants and the reaction temperature. When the reaction was performed at 50°C for 36 h with 50 mmol ester and 100 mmol amine, the product was obtained in a 97.1% yield. With 50 mmol ester and 150 mmol amine, the highest yield (97.3%) was obtained after 16 h of incubation at 50°C. It took only 5 h to get a yield of 95.8% at 60°C using 50 mmol ester and 200 mmol amine. The enzyme activity in the amidation reaction mixture did not decrease notably even after six uses.

Journal of the Serbian Chemical Society, 2011

Sixteen hydroxychalcones were synthesized in sufficient purity by the Claisen-Schmidt condensatio... more Sixteen hydroxychalcones were synthesized in sufficient purity by the Claisen-Schmidt condensation between appropriate acetophenones and aromatic aldehydes. All the compounds were evaluated for their ability to scavenge the stable free 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Important structure-activity relationships were observed that strongly contribute to the knowledge for the design of DPPH radical scavenging chalcones. Relevant theoretical parameters were computed in an attempt to understand and explain the obtained experimental results.

Bioscience, Biotechnology, and Biochemistry, 2008

Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARgamma agon... more Mycophenolic acid (MPA, 1), an inhibitor of IMP-dehydrogenase (IMPDH) and a latent PPARgamma agonist, is used as an effective immunosuppressant for clinical transplantation and recently entered clinical trials in advanced multiple myeloma patients. On the other hand, suberoylanilide hydroxamic acid (SAHA), a non-specific histone deacetylase (HDAC) inhibitor, has been approved for treating cutaneous T-cell lymphoma. MPA seemed to bear a cap, a linker, and a weak metal-binding site as a latent inhibitor of HDAC. Therefore, the hydroxamic acid derivatives of mycophenolic acid having an effective metal-binding site, mycophenolic hydroxamic acid (MPHA, 2), 7-O-acetyl mycophenolic acid (7-O-Ac MPHA, 3), and 7-O-lauroyl mycophenolic hydroxamic acid (7-O-L MPHA, 4) were designed and synthesized. All these compounds inhibited histone deacetylase with IC50 values of 1, 0.9 and 0.5 microM, and cell proliferation at concentrations of 2, 1.5 and 1 microM, respectively.

Natural Product Research, 2010

The surface metabolic composition of berries, collected from the Bulgarian grapevine variety Stor... more The surface metabolic composition of berries, collected from the Bulgarian grapevine variety Storgozia, and 12 of its seedlings were studied by GC/MS. Diverse surface metabolites were identified. The main components were long chain n-alkanes, terpenoids, and esterified long-chain fatty acids. Amongst them, the terpenoids were most abundant, including, as are typical for plants, sesquiterpenoids, diterpenoids and triterpenoids. Cyperene, a sesquiterpene hydrocarbon, was identified for the first time in grapes. This compound and most of the other identified metabolites are known to possess biological functions that most probably contribute to the quality of grape berries and their defences against biotic and abiotic stressors.

Tetrahedron: Asymmetry, 2004

Chirazyme L-2 (Candida antarctica) catalyzed esterification of glycerol with aromatic and aliphat... more Chirazyme L-2 (Candida antarctica) catalyzed esterification of glycerol with aromatic and aliphatic anhydrides in 1,4dioxane is described. All the aromatic monoacylglycerols (MAGs) were produced as (R)-enantiomers, while aliphatic MAGs were obtained either as racemic mixtures or the (S)-enantiomers. The influence of substituted aromatic rings, chain length, and presence of a conjugated double bond in the acyl donor moiety on the enantiotopic selectivity as well as the efficiency of the enzyme was studied.

European Journal of Medicinal Chemistry, 2007

A large series of chalcones were synthesized and studied for activity against Candida albicans. T... more A large series of chalcones were synthesized and studied for activity against Candida albicans. The SAR analysis showed that the antifungal activity was highly dependent on the substitution pattern of the aryl rings and correlated to a large extent with the ability of compounds to interact with sulfhydryl groups. The most active were the hydroxylated chalcones as their activity related to the location of the phenolic group in the aryl ring B as follows: o-OH > p-OH w 3,4-di-OH > m-OH. These and other correlations obtained strongly contribute to the knowledge for design of anticandidal chalcones.

Natural Product Research, 2008

Surface leaf metabolites of two seedlings of a Bulgarian winemaking cultivar Storgozia I1 were an... more Surface leaf metabolites of two seedlings of a Bulgarian winemaking cultivar Storgozia I1 were analyzed in two seasons – summer (July) and autumn (October). The resistance towards some fungal pathogens of one of the plants was estimated as superior to the resistance of the other one. Significant seasonal variations in the chemical constituents of the two seedlings were observed. The

Polish journal of microbiology / Polskie Towarzystwo Mikrobiologów = The Polish Society of Microbiologists, 2008

The antibacterial activity of synthetic aliphatic and aromatic monoacylglycerols (MAGs) was studi... more The antibacterial activity of synthetic aliphatic and aromatic monoacylglycerols (MAGs) was studied against two human pathogens: Staphylococcus aureus and Escherichia coli. The active compounds inhibited selectively S. aureus. The most active compounds amongst them were those with medium size aliphatic chain and aromatic MAGs with electron withdrawing substituents at the aryl ring. The introduction of one or two-carbon spacer between the aryl ring and the carboxylic function did not influence antibacterial effectiveness.

European Journal of Medicinal Chemistry, 2008

We reported the synthesis, antifungal evaluation and study on substituent effects of 21 chalcones... more We reported the synthesis, antifungal evaluation and study on substituent effects of 21 chalcones. A lot of genetically defined strains belonging to different yeast genera and species, namely Saccharomyces cerevisiae, Hansenula polymorpha and Kluyveromyces lactis, were used as test organisms. Concerning the mode of the antifungal action of chalcones it was shown that DNA was probably not the main target for the chalcones. It was revealed that the yeast's intracellular glutathione and cysteine molecules play significant role as defence barrier against the chalcone action. It was also shown that chalcones may react with some proteins involved in cell separation.

Kinetics and Catalysis, 2010

Six antioxidants from the class of chalcones (ArOH), compounds from which flavonoids are obtained... more Six antioxidants from the class of chalcones (ArOH), compounds from which flavonoids are obtained in nature, were studied. The antiradical activity of chalcones and a number of related compounds was determined by a chemiluminescence method using the scavenging of peroxide radicals ROO • + ArOH → ROOH + OAr • (with the rate constant k 7 ) in a model reaction of diphenylmethane (RH) oxidation. The structures and energies of the reagents and intermediates were determined by semiempirical quantum chem ical (PM3, PM6) calculations. 3,4 Dihydroxychalcone and caffeic acid, which have a catechol structure, that is, two neighboring OH groups in phenyl ring B, exhibited high antioxidant activity (k 7 ≈ 10 7 l mol -1 s -1 ); this is consistent with the lowest bond strengths D(ArO-H) of 79.2 and 76.6 kcal/mol, respectively. The abstrac tion of a hydrogen atom by the ROO • radical is the main reaction path of these compounds; however, the low stoichiometric coefficients of inhibition (f = 0.3-0.7) suggest a contribution of secondary and/or side reac tions of ArOH and OAr • . In the other chalcones, the ArO-H bond is stronger (D(ArO-H) = 83-88 kcal/mol) and the antioxidant activity is lower (k 7 = 10 4 -10 5 l mol -1 s -1 ).