Synthesis and Anti-HIV Activity of 1,1'-Dideoxygossypol and Related Compounds

• Published in: Journal of medicinal chemistry 1995-06, Vol.38 (13), p.2427-2432
• Main Authors: Royer, Robert E, Deck, Lorraine M, Vander Jagt, Timothy J, Martinez, Francella J, Mills, Ray G, Young, Stephen A, Vander Jagt, David L
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Gossypol - analogs & derivatives; Gossypol - chemical synthesis; Gossypol - metabolism; Gossypol - pharmacology; HIV-1 - drug effects; HIV-1 - physiology; human immunodeficiency virus; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Protein Binding; Serum Albumin - metabolism; Virus Replication - drug effects
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00013a018

1,1'-Dideoxygossypol (DDG), 1,1'-dideoxygossylic acid (DDGA), 8-deoxyhemigossypol (DHG), and 8-deoxyhemigossylic acid (DHGA) were synthesized and tested for their ability to inhibit the replication of HIV in vitro. The EC50 for DDGA was < 1 microM, and its threshold cytotoxicity was approximately 20 microM. DDG was less effective than DDGA against HIV and showed considerable toxicity at 5 microM. DHGA was ineffective against HIV and had very low cytotoxicity. DHG showed some anti-HIV activity, but the threshold cytotoxicity was 5 microM. The dissociation constants for the binding of the four compounds to human serum albumin were determined by fluorescence quenching titrations, and all four were found to have much lower affinities for albumin than the parent compound gossypol.