PF1270A, B and C, novel histamine H3 receptor ligands produced by Penicillium waksmanii PF1270.
Three novel histamine H3 receptor (H3R) ligands, PF1270A (1), PF1270B (2) and PF1270C (3) were isolated from the culture broth of the fungal strain PF1270. The strain was identified as Penicillium waksmanii on the basis of morphological characteristics. These compounds were obtained from the culture broth by solvent extraction and chromatographic purification. Their structures were established by spectroscopic methods and X-ray crystallographic analysis. They possess pentacyclic spiroindolinone skeletons. 1, 2 and 3 displayed high affinity for the rat H3R (Ki=0.058, 0.17 and 0.19 microM, respectively) and human H3R (Ki=0.047, 0.12 and 0.22 microM, respectively). Moreover, 1, 2 and 3 acted as potent agonists with the EC50 values of 0.12, 0.15 and 0.20 microM, respectively.
Kushida
Nobuaki
N
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, Kohoku-ku, Yokohama 222-8567, Japan. nobuaki_kushida@meiji.co.jp
Watanabe
Naoko
N
Okuda
Takako
T
Yokoyama
Fumikazu
F
Gyobu
Yasuhiro
Y
Yaguchi
Takashi
T
D000818:Animals; D001952:Bridged-Ring Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002965:Classification; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D005285:Fermentation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D013058:Mass Spectrometry; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D008968:Molecular Conformation; D010407:Penicillium / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000235:genetics; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001952:Bridged-Ring Compounds; D006575:Heterocyclic Compounds, 3-Ring; D008024:Ligands; C527226:PF1270A; C527228:PF1270B; C527227:PF1270C; D018100:Receptors, Histamine H3; D016244:Guanosine 5'-O-(3-Thiotriphosphate)