Molecular Docking Studies of Novel Thiosemicarbazone-based Indoles as Potential PI3Kα Inhibitors

Background: Heterocyclic system is a common structure feature of widely used drugs such as anticancer, anticonvulsant, antieplipeptic, and antiparastic agents. Methods: Structure-based drug design and Glide docking studies were employed to rationalize the toxicity of a new series of thiosemicarbazone-based indole derivatives against human colon carcinoma (HCT116) cell line. Results: Glide docking studies showed that the verified compounds fit PI3Kα kinase catalytic site and form H-bonding with K802, Y836, V851, S854, Q859, S919, and D933. The pharmacophore modeling of PI3Kα active inhibitors displayed that verified compounds matched four out of five functionalities of PI3Kα inhibitors. Conclusion: Our findings suggest that further optimization of the core structure of this series would be beneficial for colon cancer treatment.