ABSTRACT
A library of novel 3-trifluoromethyl pyrazolo-1,2,3-triazole hybrids (5-7) were accomplished starting from 5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-amine (1) via key intermediate 2-azido-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)acetamide (3) through click chemistry approach. Thus obtained compounds in 5-7 series were evaluated for in vitro antimycobacterial activity against Mycobacterium smegmatis (MC(2) 155) and also verified the cytotoxicity. These studies engendered promising lead compounds 5q, 7b and 7c with MIC (µg/mL) values 15.34, 16.18 and 16.60, respectively. Amongst these three compounds, 2-(4-(4-methoxybenzoyl)-1H-1,2,3-triazol-1-yl)-N-(5-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) acetamide (5q) emerged as the most promising antitubercular agent with lowest cytotoxicity against the A549 cancer cell line. This is the first report to demonstrate the pyrazolo triazole hybrids as potential antimycobacterial agents.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Mycobacterium smegmatis/drug effects , Pyrazoles/chemistry , Pyrazoles/pharmacology , Triazoles/chemistry , Triazoles/pharmacology , Anti-Bacterial Agents/chemical synthesis , Cell Line, Tumor , Click Chemistry , Halogenation , Humans , Microbial Sensitivity Tests , Models, Molecular , Mycobacterium Infections, Nontuberculous/drug therapy , Pyrazoles/chemical synthesis , Structure-Activity Relationship , Triazoles/chemical synthesisABSTRACT
A number of 3-hydroxy-6-(hydroxymethyl)-2-(2-phenyl-4H-chromen-4-yl)-4H-pyran-4-ones (3) have been synthesized in a one pot catalyst free reaction of 2-hydroxy chalcone (1) with kojic acid (2) in toluene at reflux temperature and evaluated for antimicrobial and anti-biofilm activities. Compounds 3a, 3e, 3f, 3l showed potent antimicrobial activity against Staphylococcus aureus MLS-16 MTCC 2940, Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, whereas 3b and 3k exhibited excellent activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739, while 3g showed promising activity against Bacillus subtilis MTCC 121 and Escherichia coli MTCC 739. On the other hand, compounds 3a, 3b and 3l showed very good anti-biofilm activity and 3g showed moderate activity against Bacillus subtilis MTCC 121. Whereas, compounds 3a and 3f showed moderate activity against Escherichia coli MTCC 739, while compounds 3a, 3b, 3k and 3l displayed similar activity against Staphylococcus aureus MLS-16 MTCC 2940.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Benzopyrans/pharmacology , Biofilms/drug effects , Escherichia coli/drug effects , Pyrones/chemistry , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Benzopyrans/chemical synthesis , Benzopyrans/chemistry , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Models, Molecular , Molecular StructureABSTRACT
Regioselective synthesis of a number of highly functionalized 3-benzylpyrimidino chromen-2-ones (4) were accomplished in a one pot three component reaction in acetic acid and determined their anti-microbial and anti-biofilm activities. Compounds 4o and 4p showed an excellent anti-microbial activity against Micrococcus luteus MTCC 2470 at a par with standard control (Ciprofloxacin) and exhibited best activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121. Further, compounds 4h, 4i, 4m, 4n and 4q showed promising activity against Micrococcus luteus MTCC 2470, Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121. Whereas, compounds 4m showed very promising biofilm inhibition activity against Staphylococcus aureus MLS 16 MTCC 2940 and 4o, 4p showed very potent activity against Staphylococcus aureus MTCC 96 at a par with Ciprofloxacin used as standard control.
Subject(s)
Anti-Infective Agents/chemistry , Benzopyrans/chemistry , Biofilms/drug effects , Pyrimidines/chemistry , Anti-Infective Agents/pharmacology , Bacillus subtilis/drug effects , Bacillus subtilis/physiology , Benzopyrans/pharmacology , Biofilms/growth & development , Ciprofloxacin/chemistry , Ciprofloxacin/pharmacology , Drug Evaluation, Preclinical/methods , Microbial Sensitivity Tests/methods , Micrococcus luteus/drug effects , Micrococcus luteus/physiology , Pyrimidines/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A series of fluorinated tetrahydropyrano[3,2-c]chromenes and dihydropyrano[3,2-b]pyran derivatives have been synthesized and their in vitro cytotoxic activities have been determined in cervical cancer cell line (HeLa), human breast adenocarcinoma cell line (MDA-MB-231 and MCF-7) and human alveolar adenocarcinoma cell line (A549). Compounds 4g, 4k, 4p showed a very potent activity against MDA-MB-231, and 4c, 4p showed promising activity against MCF-7, while compounds 4c, 4g, 4p showed moderate activity against HeLa.
