Benzomalvins, new substance P inhibitors from a Penicillium sp.
In the course of screening microbial broths for neurokinin receptor antagonists, a series of new benzodiazepines, benzomalvins A (1), B (2) and C (3), has been isolated from the culture broth of a fungus identified as a Penicillium sp. Benzomalvin A (1) showed inhibitory activity against substance P with Ki values of 12, 42 and 43 microM at the guinea pig, rat and human neurokinin NK1 receptors, respectively. Benzomalvins B (2) and C (3) were only weakly active. The structures of these compounds were determined by spectroscopic methods including MS measurements and NMR analysis.
Sun
H H
HH
Sterling Winthrop Pharmaceuticals Research Division, Malvern, Pennsylvania 19355.
Barrow
C J
CJ
Sedlock
D M
DM
Gillum
A M
AM
Cooper
R
R
D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010407:Penicillium / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013373:Substance P / Q000037:antagonists & inhibitors*
D011744:Pyrimidinones; D001569:Benzodiazepines; C088520:benzomalvin A; C088521:benzomalvin B; C088522:benzomalvin C; D013373:Substance P