In silico Analysis of Anticancer Curcumin and its Metabolites in increasing the effectiveness of Paclitaxel

Abstract

Curcuminoids are widely known to have biological activities such as antioxidant, anti-inflammatory, antiarthritis and anticancer. Even the use of curcumin has reached the first stage of clinical trials in overcoming a number of cancers. Interestingly, a number of curcumin metabolites also have anticancer effects that are equivalent to or even better than curcumin through a series of preclinical tests, but the description of their molecular interactions is still very limited so that in silico evidence is needed. QSAR and Molecular Docking were used as test methods using MOE 2008 software version 10. The research material was a 3D structure of curcumin derivative for QSAR analysis and curcumin metabolites for molecular docking analysis. Receptors downloaded from www.rscb.org include the 3D structure of MAPK, Akt, MDM2, NFkB, Cox-2, and VEGF, while the 3D structure of “human tubulin -1” was obtained from modeling. The QSAR results show that the anticancer activity of curcumin metabolites is stronger than curcumin except for dihydrocurcumin. The docking results also show that curcumin metabolites have the same affinity, even stronger than curcumin and control receptors with docking scores between 10-16kcal/mol. Curcumin and its metabolites were also able to increase the affinity of paclitaxel to the "human tubulin -1" receptor model as the target of paclitaxel's action which was characterized by an increase in the post-combination paclitaxel decking score. This study shows that curcumin is very suitable to be used as an anticancer because not only curcumin, but its metabolites also show better anticancer abilities.