Design, Synthesis, Molecular Docking, Anti-proliferative and Anti-TB studies of 2H-chromen-8-azaspiro[4.5]decane-7,9-dione conjugates

Abstract In this work, a series of new 8-[(substituted 2-oxo-2H-chromen-4-yl)methyl]-8-azaspiro[4.5]decane-7,9-dione derivatives (1a - 1l) is synthesized and characterized by 1H NMR, 13C NMR, FT-IR, GC-MS and elemental analysis. In addition, the structure of compound 1k has been elucidated using single crystal X-ray diffraction techniques. The synthesized compounds are screened for their anticancer and anti-TB activity. Preliminary anticancer results showed that compounds (1a- 1l) exhibit moderate to potent activity against MDA-MB-231, A549, HT-29 and Hela cancer cell lines. Compound 1f exhibited the most potent activity against MDA-MB-231cell line with IC50 value of 9.05 µM concentration, compound 1g and 1h showed potent activity against A549 cell line with IC50 value of 7.05 and 13.31 µM concentration respectively. Compound 1j showed good cytotoxicity against Hela cell line with IC50 of 16.14 µM, whereas, compound 1l is found to be moderately active against HT-29 cell line with IC50 of 18.07 µM. Anti-tubercular activity revealed that compound 1c, 1d, 1g, 1h and 1j have significant activity against MTBH37Rv strain with MIC 0.78, 1.56, 0.19, 0.39 and 0.78 µg/mL respectively. Further, to investigate the mechanism of anti-TB activity and detailed intermolecular interactions between the synthesized compounds, molecular docking studies are performed.