New Brominated and Halogen-less Derivatives and Structure-activity Relationship of Azaphilones Inhibiting gp120-CD4 Binding

• Published in: Journal of antibiotics Vol. 51; no. 11; pp. 1004 - 1011
• Main Authors: MATSUZAKI, KEIICHI, TAHARA, HARUMI, INOKOSHI, JUNJI, TANAKA, HARUO, MASUMA, ROKURO, OMURA, SATOSHI
• Format: Journal Article
• Language: English
• Published: TOKYO JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 01.11.1998; JAPAN ANTIBIOT RES ASSN; Japan Antibiotics Research Association
• Subjects: AIDS/HIV; Benzopyrans - chemistry; Benzopyrans - isolation & purification; Benzopyrans - pharmacology; Biological and medical sciences; Biotechnology & Applied Microbiology; CD4 Antigens - metabolism; Fermentation; General pharmacology; HIV Envelope Protein gp120 - metabolism; Hydrocarbons, Brominated - isolation & purification; Hydrocarbons, Brominated - pharmacology; Immunology; Life Sciences & Biomedicine; Medical sciences; Microbiology; Penicillium; Penicillium multicolor; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Science & Technology; Stereoisomerism; Structure-Activity Relationship; TAXONOMY; ISOCHROMOPHILONE-II; PENICILLIUM MULTICOLOR FO-2338; BIOLOGICAL-ACTIVITY; TALAROMYCES-LUTEUS; FERMENTATION; STRUCTURE ELUCIDATION; Fungi; Structure activity relation; P Glycoprotein; Microorganism culture; Fungi Imperfecti; Fermentation; In vitro; Thallophyta; Structural analysis; Circular dichroism
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.51.1004

Novel brominated and halogen-less azaphilone (oxoisochromane) derivatives, 5-bromoochrephilone and dechloroisochromophilone IV, and known derivatives, dechloroisochromophilone III and isorotiorin, were isolated from the culture broth of a producing organism of isochromophilones I and II (azaphilones inhibiting gp120-CD4 binding), Penicillium multicolor FO-2338, fermented in a medium containing potassium bromide. Nineteen azaphilone-related compounds isolated from the above strain and from other fungi were tested for the inhibition of gp120-CD4 binding and the structure-activity relationship is discussed. Consequently, 5-bromoochrephilone is the strongest inhibitor (IC50, 2.5 μM). A halogen atom at C-5, a proton at C-8 and a diene structure in C-3 side chain of 6-oxoisochromane ring are necessary for gp120-CD4 binding.