Synthesis, structure-activity relationship, docking and molecular dynamic simulation of curcumin analogues against HL-60 for anticancer agents (leukemia)

Abstract

Cancer such as leukemia is one of the dangerous diseases in the world. New agents with high activities are needed to attack this cancer. In this research, it was divided into three stages: synthesis, biological assay and computational approach such as molecular docking, molecular dynamic and structure activity (SAR) studies to ensure the biological activity. Synthesis of 45 curcumin analogues has been done using base or acid catalyzed aldol condensation reaction. The biological activities human promyelocytic leukemia cells line (HL-60) of those 45 curcumin analogues were investigated using 48-hour continuous exposure MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay technique and Genetic algorithm technique in Autodock 4.0 was used for molecular docking. Based on biological assay results, eight of curcumin analogues (i.e. compound 5, 8, 11, 14, 17, 28, 34 and 41) are found to be active against HL-60. From the molecular docking studies, the results showed that eight of these curcumin analogues were highly potent against HL-60 for anticancer. Finally, docking studies and MD showed that the presence of the hydroxyl group in the meta position can enhance the biological activity of compounds.