PF1270A, B and C, Novel Histamine H3 Receptor Ligands Produced by Penicillium waksmanii PF1270

Three novel histamine H3 receptor (H3R) ligands were isolated from the culture broth of the fungal strain PF1270 and displayed high affinity for the rat H3R, and acted as potent agonists with the EC50 values of 0.12, 0.15 and 0.20 μM.

Abstract

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.