A NOVEL CLASS OF PLATELET ACTIVATING FACTOR ANTAGONISTS FROM Phoma sp

• Published in: Journal of antibiotics Vol. 46; no. 4; pp. 554 - 563
• Main Authors: CHU, MIN, TRUUMEES, IMBI, GUNNARSSON, IJI, BISHOP, W. ROBERT, KREUTNER, WILLIAM, HORAN, ANN C., PATEL, MAHESH G., GULLO, VINCENT P., PUAR, MOHINDAR S.
• Format: Journal Article
• Language: English
• Published: TOKYO JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1993; JAPAN ANTIBIOT RES ASSN; Japan Antibiotics Research Association
• Subjects: Animals; Biological and medical sciences; Biotechnology & Applied Microbiology; Bones, joints and connective tissue. Antiinflammatory agents; Culture Media; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Fermentation; Fungi - chemistry; Fungi - growth & development; Fungi - metabolism; Guinea Pigs; Humans; Immunology; Life Sciences & Biomedicine; Male; Medical sciences; Microbiology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phoma; Platelet Activating Factor - antagonists & inhibitors; Rabbits; Science & Technology; Structure-Activity Relationship; MICROBIAL PRODUCTS; RABBIT; FACTOR PAF ANTAGONISTS; DITERPENE; FR-900452; Respiratory disease; Fermentation; In vitro; Biological activity; Antiallergic; Platelet activating factor; Fungi; Aggregation; Non steroidal antiinflammatory agent; Bronchospasm; In vivo; Bronchoconstriction; Chemotherapy; Platelet; Phoma; Treatment; Microbial origin; Structure activity relation; Animal; Isolation; Fungi Imperfecti; Antagonist; Physicochemical properties; Thallophyta
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.46.554

Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation in vitro with an IC50 of 1.26 μM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.