Synthesis Characterization and In silico Anticancer Activity of D-ring Substituted Steroidal Pyrazolecarboxamides

In the present study, a few D ring substituted pyrazolecarboxamide derivatives were synthesized from the key intermediate 2,3-dihydrothiopyrano[3,2-c]thiochromen-4(5H)-one(2). In order to determine the structure-activity relationships, the pyrazolecarboxamide derivatives (7 a-m) were analyzed for anticancer activity and molecular docking studies were carried out against two cancer cell lines (HeLa and HCT116). The structures of all these compounds have treating been elucidated on the basis of their spectral data. We performed docking studies with the selective inhibitor proteins 4J96 (HeLa) and 5FGK (HCT 116). The binding energy of compound 7k (-9.6 Kcal/mol-HeLa and -10.1 Kcal/mol-HCT116) was found to be lower than that of all other pyrazole derivatives as well as standard doxorubicin. Furthermore, compound 7k was also found to be a promising anticancer agent against 4J96 and 5FGK cells, given its significant inhibitory effect [IC50=20.56μM (HeLa) and 18.19μM (HCT116)] compared to doxorubicin [IC50=21.32 μM (HeLa) and 19.58 μM (HCT116)]. Hence it is understood that, the pyrazole carboxamide derivatives (7k) has selectivity for inhibitor proteins having anticancer activity against HeLa and HCT116 compared with doxorubicin.