Curcumin, a polyphenolic natural product, exhibits therapeutic activity against a number of diseases, attributed mainly to its
chemical structure and unique physical, chemical, and biological properties. It is a diferuloyl methane molecule [1,7-bis (4-hydroxy-3-
methoxyphenyl)-1,6-heptadiene-3,5-dione)] containing two ferulic acid residues joined by a methylene bridge. It has three important
functionalities: an aromatic o-methoxy phenolic group, α, β-unsaturated β-diketo moiety and a seven carbon linker. Extensive research in
the last two decades has provided evidence for the role of these different functional groups in its crucial biological activities.
A few highlights of chemical structural features associated with the biological activity of curcumin are: The o-methoxyphenol group and
methylenic hydrogen are responsible for the antioxidant activity of curcumin, and curcumin donates an electron/ hydrogen atom to reactive
oxygen species. Curcumin interacts with a number of biomolecules through non-covalent and covalent binding. The hydrogen bonding
and hydrophobicity of curcumin, arising from the aromatic and tautomeric structures along with the flexibility of the linker group are
responsible for the non-covalent interactions. The α, β-unsaturated β-diketone moiety covalently interacts with protein thiols, through
Michael reaction. The β-diketo group forms chelates with transition metals, there by reducing the metal induced toxicity and some of the
metal complexes exhibit improved antioxidant activity as enzyme mimics. New analogues with improved activity are being developed
with modifications on specific functional groups of curcumin. The physico-chemical and structural features associated with some of the
biological activities of curcumin and important analogues are summarized in this article.