Derivatization of Rosmarinic Acid Enhances its in vitro Antitumor, Antimicrobial and Antiprotozoal Properties (original) (raw)
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Journal of Food Biochemistry, 2018
Rosmarinic acid (RA), commonly found in Nepetoidae subfamily of Lamiaceae family, possesses various biological activities. To expand its application, RA was modified by esterification with methyl (me), propyl (pro), and hexyl (hex) alcohols and then tested antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. Consequently, RA derivatives enhanced antibacterial activity, especially the RA-pro and RA-hex, which effectively inhibited the growth of Bacillus cereus rather than tannic acid, a natural antibacterial agent. RA-hex also inhibited α-glucosidase inhibitory activity greater than luteolin. By computational molecular docking, dihydroxyphenyl group and hexyl group were selected as essential groups for interaction with the active site of α-glucosidase through hydrogen bonding and hydrophobic interaction, contributing to the great inhibitory activity. Furthermore, RA-pro and RA-hex effectively suppressed lipid accumulation of 3T3-L1 cells, superior to EGCG, a well-known anti-obesity phytochemical. These biological effects of RA derivatives commonly attributed to hydrophobicity, hydrogen bonding, and steric bulkiness of the side chain. Practical applications Rosmarinic acid (RA), a fundamental compound in the family Lamiaceae, is one of powerful naturally occurring antioxidants as well as other biological activities. Furthermore, its abundance in nature was also high in amount in the plant kingdom. So, natural RA can be one of possible natural resources for creating potent natural drugs and biologically useful substances after chemical modification. Studies on various biological activities may intensively expand usage and application of RA. In this study, RA was derivatized to corresponding ester such as methyl, propyl, and hexyl alcohols with higher hydrophobicity, and found great antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities. RA-pro and RA-hex significantly suppressed lipid accumulation and cell differentiation. Therefore, RA
Rosmarinic acid and its derivatives: biotechnology and applications
Critical Reviews in Biotechnology, 2012
Rosmarinic acid (RA) is one of the first secondary metabolites produced in plant cell cultures in extremely high yields, up to 19% of the cell dry weight. More complex derivatives of RA, such as rabdosiin and lithospermic acid B, later were also obtained in cell cultures at high yields. RA and its derivatives possess promising biological activities, such as improvement of cognitive performance, prevention of the development of Alzheimer's disease, cardioprotective effects, reduction of the severity of kidney diseases and cancer chemoprevention. The TNF-αinduced NF-κB signaling pathway has emerged as a central target for RA. Despite these impressive activities and high yields, the biotechnological production of these metabolites on an industrial scale has not progressed. We summarized data suggesting that external stimuli, the Ca 2+ -dependent NADPH oxidase pathway and processes of protein phosphorylation/dephosphorylation are involved in the regulation of biosynthesis of these substances in cultured plant cells. In spite of growing information about pathways regulating biosynthesis of RA and its derivatives in cultured plant cells, the exact mechanism of regulation remains unknown. We suggest that further progress in the biotechnology of RA and its derivatives can be achieved by using new high-throughput techniques.
ROSMARINIC ACID: A REVIEW OF ITS ANTICANCER ACTION
Rosmarinic acid is an ester of caffeic acid and 3,4-dihydroxyphenyl lactic acid commonly found in plants belonging to the Boraginaceae and the subfamily Nepetoideae of the Lamiaceae family. The compound has a number of important biological activities, e.g. antiviral, antibacterial, antiinflammatory, anticancer and antioxidant.
Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review
Applied Sciences
Naturally occurring food-derived active ingredients have received huge attention for their chemopreventive and chemotherapy capabilities in several diseases. Rosmarinic acid (RA) is a caffeic acid ester and a naturally-occurring phenolic compound in a number of plants belonging to the Lamiaceae family, such as Rosmarinus officinalis (rosemary) from which it was formerly isolated. RA intervenes in carcinogenesis through different ways, including in tumor cell proliferation, apoptosis, metastasis, and inflammation. On the other hand, it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects. The present review aims to provide an overview on anticancer activities of RA and to deliberate its therapeutic potential against a wide variety of diseases. Given the current evidence, RA may be considered as part of the daily diet in the treatment of several diseases, with pre-determined doses avoiding cytotoxicity.
Synthesis, Surface Activity, and Biological Activities of Phosphonium and Metronidazole Salts
Journal of Surfactants and Detergents, 2020
A series of phosphonium amphiphilic compounds was synthesized. Cationic parts of molecules contain triphenylphosphonium moieties. Lipophilic parts of compounds are represented by straight alkyl chain or the alkyl chains which are ornamented by benzyl or metronidazole. The physicochemical properties of phosphonium amphiphilic compounds were investigated by the measurements of surface tension and conductivity. The critical micelle concentration (cmc), the surface tension value at the cmc (γ cmc), the surface area at the surface saturation per head group (A cmc) were determined. The lowest cmc value was determined for phosphonium salts with straight dodecyl alkyl chain. Its value was 1.5 × 10 −3 mol dm −3. Surface tension at the cmc decreases with the addition of bulky moieties (benzyl, radical from metronidazol) at the end of alkyl chains. Biological activities of compounds were studied on human erythrocytes and strains of Acanthamoeba lugdunensis and Acanthamoeba quina. Dodecyltriphenylphosphonium bromide showed the highest activity against Acanthamoeba. To the best of our knowledge, it is the first compound of the group of phosphonium amphiphiles, which exhibited high activity against Acanthamoeba. The determined structure-activity relationship indicated nonspecific trophocidal and hemolytic activity that depends on physicochemical properties of the studied compounds.
Revista Brasileira de Farmacognosia
Since ancient times, viruses such as dengue, herpes, Ebola, AIDS, influenza, chicken meat, and SARS have been roaming around causing great health burdens. Currently, the prescribed antiviral drugs have not cured the complications caused by viruses, whereas viral replication was not controlled by them. The treatments suggested are not only ineffectual, but also sometimes inefficient against viruses at all stages of the viral cycle as well. To fight against these contagious viruses, people rely heavily on medicinal plants to enhance their innate and adaptive immune systems. In this research, the preparation of ligands and proteins was performed using the Maestro V.13.2 module tool. This software, consisting of LigPrep, Grid Generation, SiteMap, and Glide XP, has each contributed significantly to the preparation of ligands and proteins. Ultimately, the research found that (R)-(+)-rosmarinic acid was found to have significant docking scores of − 10.847 for herpes virus, of − 10.033 for NS5, and − 7.259 for NS1. In addition, the Prediction of Activity Spectra for Substances (PASS) server indicates that rosmarinic acid possesses a diverse spectrum of enzymatic activities, as probability active (Pa) values start at > 0.751, whereas it has fewer adverse effects than the drugs prescribed for viruses. Accordingly, it was found the rate of acute toxicity values of (R)-(+)-rosmarinic acid at doses LD 50 log10 (mmol/g) and LD 50 (mg/g) in different routes of administration, such as intraperitoneal, intravenous, oral, and subcutaneous. Ultimately, the present study concluded that (R)-(+)-rosmarinic acid would expose significant antiviral effects in in vitro and in vivo experiments, and this research would be a valuable asset for the future, especially for those who wish to discover a drug molecule for a variety of viruses.
Redox Biology
Phenolic acids represent abundant components contained in human diet. However, the negative charge in their carboxylic group limits their capacity to diffuse through biological membranes, thus hindering their access to cell interior. In order to promote the diffusion of rosmarinic acid through biological membranes, we synthesized several lipophilic ester-and amide-derivatives of this compound and evaluated their capacity to prevent H 2 O 2induced DNA damage and apoptosis in cultured human cells. Esterification of the carboxylic moiety with lipophilic groups strongly enhanced the capacity of rosmarinic acid to protect cells. On the other hand, the amidederivatives were somewhat less effective but exerted less cytotoxicity at high concentrations. Cell uptake experiments, using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), illustrated different levels of intracellular accumulation among the ester-and amide-derivatives, with the first being more effectively accumulated, probably due to their extensive hydrolysis inside the cells. In conclusion, these results highlight the hitherto unrecognized fundamental importance of derivatization of diet-derived phenolic acids to unveil their biological potential.
Antibacterial and resistance modifying activity of Rosmarinus officinalis
Phytochemistry 65 3249 3254, 2004
As part of a project to characterise plant-derived natural products that modulate bacterial multidrug resistance (MDR), bioassay-guided fractionation of a chloroform extract of the aerial parts of Rosmarinus officinalis led to the characterisation of the known abietane diterpenes carnosic acid (1), carnosol (2) and 12-methoxy-trans-carnosic acid. Additionally, a new diterpene, the cis A/B ring junction isomer of 12-methoxy-trans-carnosic acid, 12-methoxy-cis-carnosic acid (5), was isolated. The major components were assessed for their antibacterial activities against strains of Staphylococcus aureus possessing efflux mechanisms of resistance. Minimum inhibitory concentrations ranged from 16 to 64 lg/ml. Incorporation of 1 and 2 into the growth medium at 10 lg/ml caused a 32-and 16-fold potentiation of the activity of erythromycin against an erythromycin effluxing strain, respectively. Compound 1 was evaluated against a strain of S. aureus possessing the NorA multidrug efflux pump and was shown to inhibit ethidium bromide efflux with an IC 50 of 50 lM, but this activity is likely to be related to the inhibition of a pump(s) other than NorA. The antibacterial and efflux inhibitory activities of these natural products make them interesting potential targets for synthesis.
Two new categories of a-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.
SYNTHESIS, CHARACTERIZATION AND BIO-ACTIVITY OF SOME NEW
ABSTRACT. A convenient and efficient one-pot reaction has been employed for the synthesis of new α- aminophosphonates 4a-4k via Kabachnik-Fields reaction in 65-82 % yields. In the procedure developed, equimolar quantities of 2-amino-4-methylphenol 1, various aromatic aldehydes 2a-2k and dimethylphosphite 3 in dry toluene were reacted under reflux for 4-6 h. The products were characterized by IR, 1H, 13C and 31P NMR spectra and elemental analysis. All the synthesized compounds were screened for in vitro antibacterial activity (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium) and antifungal activity (Candida albicans, Aspergillus niger). 4a showed potent activity with lowest MIC value.