Important chemical structural features of curcumin and its derivatives: How do they influence their anticancer activity?

Curcumin is the active component of the Indian spice turmeric, known since ancient times for medicinal properties. Extensive research in the last two to three decades has confirmed its promising pharmacological properties such as anti-cancer, anti-oxidant, anti-inflammatory etc., leading to several ongoing/completed clinical trials. Curcumin has three reactive functional groups: one diketone moiety, and two phenolic groups. Curcumin interacts with several biomolecules through non-covalent and covalent binding. However, the properties limiting its potential are low bioavailability and fast degradation. The metabolites as well as degradation products of curcumin show biological activities but not as much as curcumin. To overcome these limitations, new analogues with modifications on both o-methoxy group and the diketo structures of curcumin have been developed. Of several analogues, dimethyl curcumin, where the phenolic OH is absent showed better anti-tumor activity. Also, the isoxazole and pyrazole derivatives of curcumin, derivatized at the diketo moiety have been investigated in our group. Hispolon, which is a half curcumin analogue also showed interesting cellular activity. Here in the present manuscript, the comparative cytotoxic effect of curcumin and some of these derivatives in cancer cells is presented. The results indicated that specific structural modifications on curcumin can be adopted to fine-tune its desired anticancer activity.