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

• Published in: ChemistrySelect (Weinheim) 2017-06, Vol.2 (18), p.5234-5242
• Main Authors: Chougala, Bahubali M., S, Samundeeswari, Holiyachi, Megharaja, Naik, Nirmala S., Shastri, Lokesh A., Dodamani, Suneel, Jalalpure, Sunil, Dixit, Sheshagiri R, Joshi, Shrinivas D., Sunagar, Vinay A
• Format: Article
• Language: English
• Subjects: 2-Amino-3-cyanopyridines; Anticancer activity; BSA, CT-DNA cleavage; Fluorescence quenching study; NCI-60
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201700358

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. Catalysts free bioactive 2‐amino‐4‐(2‐oxo‐2H‐chromen‐4‐yl)‐6‐arylpyridine‐3‐carbonitrile (2 a‐2 o) have been synthesized via one‐pot four component reaction under microwave. Compounds 2 f and 2 k are exhibited promising anticancer activity against NCI‐60 cell lines. IC50 values were determined against three cancer cell lines such as HT‐29, Hep‐G2 and KB. Among the eight compounds, 2 f and 2 k were screened for their CT‐DNA cleavage and fluorescence quenching study with BSA. Molecular docking study has been performed with binding site of tubulin using podophyllotoxin‐tubulin stathmin‐like domain complex (PDB 1SA1).