Author: Sui, Z.; Salto, R.; Li, J.; Craik, C.; Ortiz de Montellano, P.R.
Description: Curcumin, a relatively non-toxic natural product isolated from Curcuma longa, is a modest inhibitor of the HIV-1 (IC50 = 100 microM) and HIV-2 (IC50 = 250 microM) 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 microM. 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 interesecting sites within the substrate-binding cavity of the enzyme, while activation of the alpha, beta-unsaturated carbonyl group of curcumin by chelation to boron probably accounts for time-dependent inhibition of the enzyme.
Subject Headings: Aspartic Acid Endopeptidases/antagonists & inhibitors/chemistry; Binding Sites; Boron/chemistry/pharmacology; Curcumin/analogs & derivatives/chemistry/pharmacology; HIV Protease/chemistry; HIV Protease Inhibitors/chemistry/pharmacology; HIV-1/drug effects/enzymology; HIV-2/drug effects/enzymology; Kinetics; Magnetic Resonance Spectroscopy; Molecular Structure; Structure-Activity Relationship
Keywords: Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes
Publication year: 1993
Journal or book title: Bioorganic & Medicinal Chemistry
Volume: 1
Issue: 6
Pages: 415-422
Find the full text : https://www.sciencedirect.com/science/article/pii/S0968089600821525
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Type: Journal Article
Serial number: 2834