QSAR, Molecular Docking and Molecular Dynamics Simulation Studies for the prediction of Camptothecin derivatives as anticancer agents

Abstract Camptothecin is a cytotoxic pyranoindolizinoquinoline alkaloid that selectively inhibits the nuclear enzyme topoisomerase I. In Present work, the 2D-QSAR, molecular docking and MD simulation studies of anticancer activity of Camptothecin derivative reported by Yang et al.,2019 has been reported. To develop the QSAR model, previously reported IC50 data of 46 CPT derivatives against Hep3B, MCF7, MDA-MB-231, and KB-vin cell lines was extracted. The models suggest that electronic and topological type descriptors are highly correlated with anticancer activity. Molecular docking of CPT derivatives against topoisomerase I revealed that compounds C40, C43, C41 and C32 have best docking score -9.13, -8.96, -8.90, and -8.53 kcal/mol respectively against topoisomerase I and showed binding affinity with residues namely LYS:532, ASN:722, DG:12, DA:113, DC:112, and DT:10. Further MD Simulation study indicated the stability of protein in topo I–C41 complex with an RMSD of 1.7 Å which makes C41 as a lead compound for the development of novel anticancer agent.