Inhibition of the HIV-1 and HIV-2 Proteases by Curcumin and Curcumin Boron Complexes

Bioorg Med Chem. 1993 Dec;1(6):415-22. doi: 10.1016/s0968-0896(00)82152-5.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / chemistry
  • Binding Sites
  • Boron / chemistry
  • Boron / pharmacology
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • HIV Protease / chemistry
  • HIV Protease Inhibitors / chemistry*
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • HIV-2 / drug effects
  • HIV-2 / enzymology*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • HIV Protease Inhibitors
  • Aspartic Acid Endopeptidases
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 2
  • Curcumin
  • Boron