Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes |
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Authors: | Zhihua Sui Rafael Salto Jia Li Charles Craik Paul R. Ortiz de Montellano |
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Affiliation: | Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446, U.S.A. |
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Abstract: | Curcumin, a relatively non-toxic natural product isolated from Curcuma longa, is a modest inhibitor of the HIV-1 (1050 = 100 μM) and HIV-2 (IC50 = 250 μM) proteases. Simple modifications of the curcumin structure raise the IC50 value but complexes of the central dihydroxy groups of curcumin with boron lower the IC50 to a value as low as 6 μM. The boron complexes are also time-dependent inactivators of the HIV proteases. The increased affinity of the boron complexes may reflect binding of the orthogonal domains of the inhibitor in intersecting sites within the substrate-binding cavity of the enzyme, while activation of the ,β-unsaturated carbonyl group of curcumin by chelation to boron probably accounts for time-dependent inhibition of the enzyme. |
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