ABSTRACT
A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 µm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 µm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis.
Subject(s)
Antineoplastic Agents/pharmacology , Chalcones/pharmacology , Drug Design , Models, Molecular , Pyrazoles/pharmacology , Triazoles/pharmacology , Tubulin Modulators/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chalcones/chemical synthesis , Chalcones/chemistry , Female , G2 Phase/drug effects , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Molecular Structure , Neoplasms/drug therapy , Neoplasms/pathology , Polymerization/drug effects , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Triazoles/chemical synthesis , Triazoles/chemistry , Tubulin/chemistry , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistryABSTRACT
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.
