Curcumin recognizes a unique binding site of tubulin

Abstract

Although curcumin is known for its anti-carcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogs, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: i) curcumin acts as a bifunctional ligand, ii) analogs with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, iii) a benzylidiene derivative (7) is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed (7) to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 Å away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure activity studies suggest that the tridented nature of (7) is responsible for its higher affinity for tubulin compared to curcumin.