Design, synthesis, cytotoxic evaluation and molecular docking studies of novel thiazolyl α-aminophosphonates

• Published in: Research on chemical intermediates 2021-03, Vol.47 (3), p.1139-1160
• Main Authors: Gundluru, Mohan, Badavath, Vishnu Nayak, Shaik, Haroon Yasmin, Sudileti, Murali, Nemallapudi, Bakthavatchala Reddy, Gundala, Sravya, Zyryanov, Grigory V., Cirandur, Suresh Reddy
• Format: Article
• Language: English
• Subjects: Amines; Anticancer properties; Aromatic compounds; Cancer; Catalysis; Chemical synthesis; Chemistry; Chemistry and Materials Science; Cyclodextrins; Cytotoxicity; Inorganic Chemistry; Molecular docking; Physical Chemistry; Reaction time; Sulfonic acid
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-020-04321-6

A new class of thiazolyl α-aminophosphonate derivatives was synthesized by one-pot Kabachnik–Fields reaction of ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate with various aryl amines and diethyl phosphite under solvent-free conditions using β-cyclodextrin supported sulfonic acid ( β -CD-SO 3 H) as an efficient, reusable and heterogeneous solid acid catalyst. The products were obtained in good to excellent yields at shorter reaction time. All the title compounds were screened for cytotoxic activity against human breast cancer (MCF-7 and MDA-MB-231), prostate cancer (DU-145) liver cancer (HepG2) and HeLa cancer cell lines using sulfarodamine-B (SRB assay). Compounds ( 8b , –4OMe), ( 8h , –4NO 2 ) and ( 8j , –2I, –4CF 3 ) showed better anticancer activity when compared with standard drug Adriamycin. Further in-silico target hunting reveals the anticancer activity of the designed compounds by inhibiting DNA topoisomerase II. Graphical abstract