Inhibitors of human immunodeficiency virus integrase.

Abstract

In an effort to further extend the number of targets for development of antiretroviral agents, we have used an in vitro integrase assay to investigate a variety of MATERIALS AND METHODS Materials. HIV-1 integrase protein (3.5 pmol per reaction), produced via an Escherichia coli expression vector as described (13), was obtained from R. Craigie (Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases) and stored at -70°C in 1 M NaCl/20 mM Hepes, pH 7.6/1 mM EDTA/1 mM dithiothreitol/20% glycerol (wt/vol). Caffeic acid phenethyl ester (CAPE) was brought to our attention by Dezider Grunberger (Columbia University, New York), who supplied the compound. Doxorubicin, 5-iminodaunorubicin, mitoxantrone, ellipticine, ellipticinium, 9-aminoacridine, amsacrine, ditercalinium, ethidium, camptothecin, 9-aminocamptothecin, 10,11-methylenedioxycamptothecin, etoposide (VP-16), teniposide (VM-26), and quercetin were obtained through the Developmental Therapeutics Program, National Cancer Institute. Hydroxyrubicin and adriamycinone were obtained through Waldemar Priebe (M. D. Anderson Hospital, Houston). Naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone, 5-hydroxy-1,4-naphthoquinone, and dihydroxyanthraquinone were purchased from Aldrich. Chloroquine, primaquine, quinacrine, and amodiaquine were obtained through Sigma. Hydroxychloroquine was from SterlingWinthrop Research Institute. Mefloquine was from Hoffmann-La Roche.Oligonucleotide Substrate. Oligonucleotides were obtained from Midland Certified Reagent (Midland, TX), and were HPLC-purified before use. The following complementary oligonucleotides were used as substrates:AE118: 5'-GTGTGGAAAATCTCTAGCAGT-3' and AE117: 5'-ACTGCTAGAGATTTTCCACAC-3' (2). 2399The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Simultaneous determination of caffeic acid phenethyl ester and its metabolite caffeic acid in dog plasma using liquid chromatography tandem mass spectrometry

“…In recent years, CAPE has attracted increasing scientific interest due to its various pharmacological activities, e.g., anticancer/tumor [2][3][4][5][6], antiviral [7,8], anti-inflammatory [9][10][11][12][13], antioxidant [14][15][16][17], cytoprotection, [18][19][20][21][22] and vasorelaxant effects [23,24]. The pharmacological effects and mechanisms of CAPE have been comprehensively reviewed recently [25].…”

Nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors: synthesis, structure-activity relationship analysis, and biological activity

“…It also exhibits significant anti-viral activity with little cytotoxicity in primary human peripheral blood mononuclear cells (PBMC) culture 6,7 . Therefore, CAPE is a potential lead for further structural optimization as potent IN inhibitors.…”

Biotransformation of Underutilized Natural Resource to Valuable Compounds in Ionic Liquid: Enzymatic Synthesis of Caffeic Acid Phenethyl Ester Analogues from Immature Coffee Beans

“…Caffeic acid phenethyl ester (CAPE) especially has been found in propolis and has a broad spectrum of biological activities, including antimicrobial, antiinflammatory, antioxidant, and antitumor activities (Bankova, 2005); it also has an inhibitory effect on HIV-1 integrase, cyclooxygenase, and lipooxygenase (Fesen et al, 1993;Michaluart et al, 1999;Nicklaus et al, 1997;Sud'ina et al, 1993). It has been reported that the ester part of CAPE is important for its antiproliferative effect on various human tumor cells (Nagaoka et al, 2003).…”