Microwave Synthesis of Coumarinyl Substituted Pyridine Derivatives as Potent Anticancer Agents and Molecular Docking Studies

Abstract

Catalyst free new bioactive 2‐amino‐4‐(2‐oxo‐2H‐chromen‐4‐yl)‐6‐arylpyridine‐3‐carbonitrile molecular entities (2 a‐2 o) have been synthesized from 4‐formylcoumarins with malononitrile, different ketones and ammonium acetate via one‐pot four component coupling reaction under neat microwave method. Detailed characterization of all the compounds and anticancer properties for the synthesized compounds are reported. Compounds 2 f and 2 k exhibited promising anticancer activity at low concentration (10−5 M) against NCI‐60 cell lines. Further, IC50 values were calculated for most potent compounds against three cancer cell lines such as HT‐29, Hep‐G2 and KB. Among the eight compounds, 2 f and 2 k are exhibited most promising activity, the potent anticancer molecules 2 f and 2 k were screened for their CT‐DNA cleavage and fluorescence quenching study with transport protein BSA. Molecular docking study has been performed for the synthesized compounds with binding site of the tubulin using podophyllotoxin‐tubulin stathmin‐like domain complex (PDB 1SA1) and results obtained are quite good.

Synthesis of Biologically Active Molecules through Multicomponent Reactions

“…All synthesized compounds presented a remarkable anticancer activity against HT29, HepG2 and KB cell lines in the range of 4.22 to 27.58 µM. Compound 179f (6-methyl on coumarin and 6-coumarin on pyridine) and 179k (6-methyl on coumarin and 6-bromocoumarin on pyridine) presented prominent antitumor activity with IC 50 values of 4.22 and 5.62 µM for HT-29, 5.02 and 6.94 µM for HepG2 and 6.82 and 9.64 µM for KB, respectively [200].…”

Coumarin‐containing hybrids and their antibacterial activities

“…The coumarin–pyrazole hybrids 10 (MIC: 0.78–50.0 µg/ml), as well as their ring closure derivatives 11 (MIC: 3.12–12.5 µg/ml) and 12 (MIC: 0.78–50.0 µg/ml), exhibited considerable activity against S. aureus , E. faecalis , E. coli , and P. aeruginosa , and a significant part of them was not inferior to ciprofloxacin (MIC: 3.12–6.25 µg/ml). [ 51 ] The SAR implied that introduction of substituents into C‐6 position of coumarin moiety could boost up the activity, and methoxy was optimal. Amongst them, hybrids 10b (MIC: 0.78–6.25 µg/ml) and 12b (MIC: 1.56–6.25 µg/ml) were two‐ to fourfold more potent than ciprofloxacin against S. aureus and E. coli , and both of them were comparable to ciprofloxacin against E. faecalis and P. aeruginosa .…”

Synthesis of Pyrimidine and Pyran Derivatives with the Related Systems and the Study of Their Behavior in the Liquid Solutions

“…Therefore, it enters into wide range of applications such as pharmaceuticals, agrochemicals, disinfectants, developers, corrosion inhibitors, and polymers as they are used in the synthesis of other organic compounds where the most majority of new drugs contains heterocycles interface between chemistry and biology . Nemours compounds containing isoxazole, pyrazole, pyrazole, and pyrimidine moieties are bioactive molecules, which play an important role in the medicinal fields because of their diverse biological and pharmacological activities as antibacterial, antifungal, antioxidant, antipyretics, anti‐inflammatory, antiviral, cytotoxic, anticancer agent, antihypertensive, muscle‐relaxant, hypnotic, antidepressant, analgesic, and antimicrobial agents . In addition, they have been widely used in agricultural chemistry because of their highly significant fungicidal, insecticidal, and herbicidal activities .…”