PAF-RECEPTOR .1. CACHE-OREILLES EFFECT OF SELECTED HIGH-POTENCY PLATELET-ACTIVATING FACTOR (PAF) ANTAGONISTS

  • 1 July 1989
    • journal article
    • research article
    • Vol. 1  (4) , 201-215
Abstract
Three-dimensional electrostatic maps were calculated for six potent antagonists of platelet-activating factor (PAF), the antagonists being selected for their apparent structural heterogeneity. The molecules examined were the compact Ginkgolides BN 52020, BN 52021 and BN 52022 (1, 2 and 3), the semi-rigid kadsurenone (4), a flexible synthetic dinor type C furanoid lignan L-652,731 (5a) and the triazolothienobenzodiazepine WEB 2086 (7). Calculation of the electrostatic potential generated around all of the above molecules showed the existence of two wells of negative potential or ''cache-oreilles'' (ear-muffs), i.e., the isocontours drawn at - 10 kcal/mol, located at 180.degree. from each other and separated by a maximum distance of 22-27 .ANG.. Except for the synthetic dinor type C furanoid lignan (5a), the molecules also presented a moderate hydrophobic fragment, which constitutes a third point of interaction with the high-affinity binding site in rabbit and human platelets. The findings of the present study allow speculation that this high-affinity acceptor site may be a ''polarized cylinder'' with a diameter of 10-12 .ANG.

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