Aconitum and Delphinium sp. alkaloids as antagonist modulators of voltage-gated Na+ channels

摘要: Early pharmacological studies of Aconitum and Delphinium sp. alkaloids suggested that these neurotoxins act at site 2 voltage-gated Na^+ channel allosterically modulate its function. Understanding structural requirements for compounds to exhibit binding activity has been important in various fields. This paper reports quantum-chemical quantitative structure-activity relationships (QSARs) based on a total 65 natural from two plant species, which includes both blockers openers sodium ion channel. A series 18 antagonist (9 9 openers) have studied using AM1 DFT computational methods order reveal their (structure-toxicity) relationship electronic level. An examination frontier orbitals obtained ground protonated forms the revealed HOMOs LUMOs were mainly represented by nitrogen atom benzyl/benzoylester with ?OH ?OCOCH"3 contributions. The results this research confirmed experimental findings suggesting acting type receptor voltage-dependent are activators common features differ only efficacy. energetic tendency HOMO-LUMO energy gap can probably distinguish observed. Genetic Algorithm Multiple Linear Regression Analysis (GA-MLRA) technique was also applied generation three-descriptor QSAR models set blockers. Additionally studies, descriptor each model crucial role charge transfer receptor-ligand interactions. number other descriptors such as logP, I"B"E"G, nNH2, nHDon, nCO selected complementary ones LUMO alteration discussed.