Designing and Development of Novel Curcumin Analogues/Congeners as Inhibitors of Breast Cancer Stem Cells Growth

Curcumin, a polyphenolic yellow pigment of the spice turmeric is a unique, multi-targeted molecule having potential for cancer therapy. The inhibition of cancer stem cell growth is an essential step for breast cancer treatment. The main objective of the present work is to identify a potential target of curcumin against breast cancer stem cells and also to predict potency of designed curcumin analogues/congeners on predicted target. The high expression level of P-glycoprotein (P-gp) in the population of breast cancer stem cells promotes the cancer stem cells growth. The anticancer activity of curcumin is directly associated with the inhibition of P-gp mediated efflux process. This efflux mechanism is considered as a major reason for the failure of multidrug resistance in the cancer treatment. Using computational tools, the strong potency of curcumin against P-gp for the inhibition of breast cancer stem cells growth has been determined. Few analogues of curcumin were found to be more effective than curcumin towards cancer stem cells inhibition. In this way, the present study provides the pathway to design and improve the efficacy of novel and therapeutically important herbal drugs for the inhibition of breast cancer stem cells via inhibiting the P-gp mediated efflux mechanism.