Insilico study of bioactive compounds having similar structure to cell death inducer natural products in Cancer

Introduction &Objectives: Vinblastine (by binding to the Tubulin protein and stopping the Microtubules formation) and Doxorubicin (by inhibiting of Topoisomerase II) induce 'programmed cell death' in cancer cells and lead to more effective treatment compare to other natural compounds in a wide range of cancers. The present study is a bioinformatics study of some other natural compounds having the structural similarity with the compounds mentioned above.Materials & Methods: Initially, natural compounds with similar structure to Vincristine and Doxorubicin were prepared from the ZINC database. After getting three-dimensional structure of tubulin (the target of similar structure ligands of Vincristine) and Topoisomerase II proteins (the target of the structurally similar ligand of Doxorubicin) with the access codes of … and 3QX3, respectively, from pdbbank, the binding affinity of the mentioned ligands with mentioned targets was determined by AutoDockTools-1.5.6 software. Finally, pharmacokinetic properties (ADMET) of ligands considered in this study were evaluated by the FAF-Drug4 server. Results: according to the results of docking studies for ligands with similar structure to Vincristine, ZINC000085537024 have the most negative binding energy (-8.18 kcal/mol) compared to ZINC000095616067 ،ZINC000085555528 and ZINC000085432544 (-5.25, -4.73 and -2.57 kcal/mol, respectively). Additionally, for the only ligand having the similar structure to doxorubicin (ZINC000003917708) the energy binding of -11.38 kcal/mol was reported. It is worth to mention that pharmacokinetic studies for all compounds showed promising results. Conclusion: regarding to the results of considered compounds, the ligand with similar structure to doxorubicin (ZINC000003917708) and Vincristine (ZINC000085537024) tend to bind with their targets more effectively. Considering the promising results of drug-likeness as well as absorption, distribution, metabolism, excretion and toxicity properties, obtained from pharmacokinetic analysis, they are the appropriate novel candidates for cancer treatment.