A novel class of platelet activating factor antagonists from Phoma sp.
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 microM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.
Schering-Plough-Research Institute, Kenilworth, NJ 07033.
M
M
Chu
I
I
Truumees
I
I
Gunnarsson
W R
WR
Bishop
W
W
Kreutner
A C
AC
Horan
M G
MG
Patel
V P
VP
Gullo
M S
MS
Puar
D000818:Animals; D003470:Culture Media; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D005658:Fungi / Q000737:chemistry* / Q000254:growth & development / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013329:Structure-Activity Relationship
D003470:Culture Media; D004224:Diterpenes; D010972:Platelet Activating Factor