Open AccessInhibition of human immunodeficiency virus integrase by bis-catechols
Author(s) -
Robert L. LaFemina,
Peter M. Graham,
K LeGrow,
J C Hastings,
Abigail Wolfe,
Steven D. Young,
Emilio A. Emini,
Daria J. Hazuda
Publication year - 1995
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.39.2.320
Subject(s) - integrase , integrase inhibitor , in vitro , biology , virology , enzyme , virus , structure–activity relationship , potency , cell culture , sequence (biology) , human immunodeficiency virus (hiv) , microbiology and biotechnology , biochemistry , genetics , viral load , antiretroviral therapy
The human immunodeficiency virus type 1 (HIV-1) integrase protein is required for the productive infection of T-lymphoid cells in culture (R. L. LaFemina, C. L. Schneider, H. L. Robbins, P. L. Callahan, K. LeGrow, E. Roth, W. A. Schleif, and E. A. Emini, J. Virol. 66:7414-7419, 1992). This observation suggests that chemical inhibitors of integrase may prevent the spread of HIV in infected individuals. In our search for such potential chemotherapeutic agents, we observed that beta-conidendrol inhibits both the sequence-dependent and sequence-independent endonucleolytic activities of integrase with comparable potencies in vitro (50% inhibitory concentration, 500 nM). Structurally related compounds tested for their abilities to inhibit integrase generated a limited structure-activity analysis which demonstrated that potency is associated with the bis-catechol structure: two pairs of adjacent hydroxyls on separate benzene rings. beta-Conidendrol did not inhibit several other endonucleases and/or phosphoryltransferases. Although beta-conidendrol was not effective in preventing HIV-1 infection in cell culture, the in vitro data demonstrate that it is possible to identify selective agents targeted against this essential HIV-1 function.