Synthesis of novel hybrid hetero-steroids: Molecular docking study augmented anti-proliferative properties against cancerous cells.

Hetero-steroids, hybrid anticancer agents, have received much interest in view of their numerous and promising biological activities. In this study, a novel class of hetero-steroids were synthesized, analytical and spectral data proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of the synthesized compounds 2, 5, 6, 7, 10, 11, 12, 14, 15, 17 were evaluated using human hepatocellular carcinoma cell lines (HepG2 and Huh-7) and non-small cell lung cancer (A549) cell lines. The synthesized compounds reported a remarkable gradual decrease in the cell viability of the three tested cancer cell lines. It was observed that compounds 2 and 12 had the lowest IC and the highest cytotoxic effects against all tested cell lines. As attempt to explain the cytotoxic activity achieved by the tested compounds in the in vitro study, molecular simulation was done to reveal the activity of the tested compounds against four different proteins (CDK2, CYP19, JAK2, and BCL2) which are highly implicated in cancer regulation and progression. We found that compound 2, and 12 were the best docked compounds against all tested receptors, which was indicated by lowest binding energy compared to reference ligand. Interestingly enough, our molecular study was in agreement with the cytotoxic activity. As future prospective, we are recommending further study on compounds 2, and 12 against the four different proteins to prove their mode of action.