Novel sulphonamide-azaheterocycle conjugates and their anti-cancer, anti-inflammatory, anti-diabetic, anti-angiogenesis activity and molecular docking studies

Abstract

The present study reports the synthesis of sulphonamide-azaheterocycle conjugates (3 a-j) and evaluates its in vitro anticancer activity against breast cancer cell line (MCF-7) and liver cancer cell line (HepG2). The compound 3g was found to be the most active compound with IC50 values of 40.54 ± 0.25 μg/ml against MCF 7 cell line and 55.38 ± 0.18 μg/ml against HepG2 cell line. The compound 3h was found to be most active with IC50 value of 36.70 ± 0.90 μg/ml against MCF 7 cell line and 54.75 ± 0.68 μg/ml against HepG2 cell line as compared to the standard drug 5-fluorouracil (26.08 ± 0.82 μg/ml and 45.50 ± 2.35 μg/ml). The compounds 3 a-j showed characteristic changes, particularly in the nucleus, which were observed through nuclear staining with the fluorescent dye DAPI. The compound 3h has shown strong anti-inflammatory activity with IC50 values of 31.17 ± 0.23 μg/ml. Furthermore, the anti-diabetic activity of 3g and 3h exhibited significant activity with IC50 values 34.51 ± 1.31 and 33.87 ± 1.54 μg/ml as compared to the standard drug acarbose. Compounds 3a, 3b, 3d, 3f, 3g and 3h displayed a strong antiangiogenic effect, with an antiangiogenic score of 1.34, 1.28, 1.32, 1.41, 1.41 and 1.45. Moreover, in silico bioactivity prediction studies demonstrated significant interactions between the compounds and putative drug targets. Results of DFT analysis highlighted that 3h possesses a favorable electronic structure with the possibility of having promising potential in biological applications. The analysis of binding affinities in docking studies highlighted that 3h exhibited the most favorable binding among all sulphonamide-azaheterocycle conjugates (3 a-j) tested against both the HER2 (PDB: 3PP0) and EGFR (PDB: 4HJO).