ABSTRACT
Most of pharmaceutical agents display several or even many biological activities. It is obvious that testing even one compound for thousands of biological activities is a practically not reasonable task. Therefore, computer-aided prediction is the method of choice for the selection of the most promising bioassays for particular compounds. Using PASS Online software, we determined the probable antimicrobial activity of the 31 steroid derivatives. Experimental testing of the antimicrobial activity of the tested compounds by microdilution method confirmed the computational predictions. Furthermore, P. aeruginosa and C. albicans biofilm formation was investigated. Compound 11 showed a biofilm reduction by 42.26% at the MIC of the tested compound. The percentages are lower than ketoconazole, but very close to its activity.
Subject(s)
Anti-Infective Agents , Antifungal Agents , Molecular Docking Simulation , Antifungal Agents/pharmacology , Structure-Activity Relationship , Anti-Bacterial Agents/pharmacology , Hydrazones/pharmacology , Quantitative Structure-Activity Relationship , Anti-Infective Agents/pharmacology , Candida albicans , Steroids/pharmacology , Microbial Sensitivity Tests , Molecular StructureABSTRACT
Herein we report the evaluation of the antimicrobial activity of some previously synthesized 3-(3,4-dihydroxyphenyl)glyceric acid in benzylated and in free 3,4 hydroxy groups in catechol moiety along with some caffeic and 3-(3,4-dihydroxyphenyl)glyceric acid amides using the microdilution method. The evaluation revealed that compounds showed in general moderate to low activity with MIC in range of 0.36-4.5 mg/mL. Compounds were also studied against three resistant bacteria strains MRSA (Methicillin-resistant Staphylococcus aureus), E. coli and P. aeruginosa. Seven out of ten compounds were more potent than reference drugs ampicillin and streptomycin against MRSA, while against another two resistant strains seven compounds showed low activity and the rest were inactive. Antifungal activity of the tested compounds was much better than antibacterial, with MIC in the range of 0.019-3.0 mg/mL. Compounds #7 and 15 showed good activity against all fungi tested, being more potent than ketoconazole and in some case even better than bifonazole used as reference drugs. Docking studies revealed that the most active compound #7 binds to the haem group of the enzyme in the same way as ketoconazole.
Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Escherichia coli , Glyceric Acids , Ketoconazole , Microbial Sensitivity Tests , Molecular Docking Simulation , Quantitative Structure-Activity Relationship , Structure-Activity RelationshipABSTRACT
Isonicotinoylhydrazones and thiosemicarbazones of some 5alpha-ketosteroids were synthesized from tigogenin, and their structures were confirmed by NMR and IR spectroscopy and mass spectrometry. Their antimycobacterial activities were studied, and it was shown that some of the synthesized isonicotinoylhydrazones exhibit a high antituberculosis activity. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 5; see also http: // www.maik.ru.