Chemistry and Structure−Activity Relationship of HIV-1 Integrase Inhibitor Integracide B and Related Natural Products

• Published in: Journal of natural products (Washington, D.C.) Vol. 66; no. 10; pp. 1338 - 1344
• Main Authors: Singh, Sheo B, Ondeyka, John G, Schleif, William A, Felock, Peter, Hazuda, Daria J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.2003; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: 4,4-dimethylergostane triterpenoids; Anti-HIV Agents - chemistry; Anti-HIV Agents - isolation & purification; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chemistry, Medicinal; Combinatorial Chemistry Techniques; HIV Integrase - metabolism; HIV Integrase Inhibitors - chemistry; HIV Integrase Inhibitors - isolation & purification; HIV Integrase Inhibitors - pharmacology; HIV-1 - drug effects; Human immunodeficiency virus 1; Inhibitory Concentration 50; integracides; Life Sciences & Biomedicine; Medical sciences; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Science & Technology; Structure-Activity Relationship; therapeutics; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; CELLS; ACID; REPLICATION; PROTEIN; IMMUNODEFICIENCY-VIRUS INTEGRASE; FUNGAL METABOLITES; STEREOCHEMISTRY; HYDROLYSIS; Steroid; Terpenoid; HIV-1 virus; Enzyme; Transferases; Retroviridae; Enzyme inhibitor; Lentivirus; In vitro; Virus; Nucleotidyltransferases; Structure activity relation; Triterpene; Antiviral; Human immunodeficiency virus; Secondary alcohol; Chemical synthesis; Acylate; Glycol
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np030211s

Integracides, 4,4-dimethylergostane triterpenoids, are inhibitors of HIV-1 integrase, a critical enzyme in replication of HIV-1. The chemistry and structure−activity relationship of integracide B and related natural products are described. A charged group, e.g., a sulfate, carboxyl, or amino, is required for the HIV-1 integrase activity. These compounds showed HIV-1 integrase activity with IC50 values in the range 4.8−15 μM and exhibited antiviral activity in a viral spread assay, but with only a small or no therapeutic window.