Aconitum and Delphinium sp. alkaloids as antagonist modulators of voltage-gated Na+ channels. AM1/DFT electronic structure investigations and QSAR studies.

Computational Biology and Chemistry
M A TurabekovaJ Leszczynski

Abstract

Early pharmacological studies of Aconitum and Delphinium sp. alkaloids suggested that these neurotoxins act at site 2 of voltage-gated Na(+) channel and allosterically modulate its function. Understanding structural requirements for these compounds to exhibit binding activity at voltage-gated Na(+) channel has been important in various fields. This paper reports quantum-chemical studies and quantitative structure-activity relationships (QSARs) based on a total of 65 natural alkaloids from two plant species, which includes both blockers and openers of sodium ion channel. A series of 18 antagonist alkaloids (9 blockers and 9 openers) have been studied using AM1 and DFT computational methods in order to reveal their structure-activity (structure-toxicity) relationship at electronic level. An examination of frontier orbitals obtained for ground and protonated forms of the compounds revealed that HOMOs and LUMOs were mainly represented by nitrogen atom and benzyl/benzoylester orbitals with -OH and -OCOCH(3) contributions. The results obtained from this research have confirmed the experimental findings suggesting that neurotoxins acting at type 2 receptor site of voltage-dependent sodium channel are activators and blockers with commo...Continue Reading

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Citations

Feb 7, 2012·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Alicja Nowaczyk, Katarzyna Kulig
May 1, 2008·Environmental Toxicology and Pharmacology·Malakhat A TurabekovaShavkat I Salikhov
Sep 17, 2014·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·M A TurabekovaJ Leszczynski
May 12, 2016·Organic Letters·Yoshitake NishiyamaTohru Fukuyama
Mar 26, 2010·Natural Product Reports·Feng-Peng WangXiao-Yu Liu
Nov 6, 2010·Bulletin of Environmental Contamination and Toxicology·Jian Lin JiangZhen Gao
Apr 5, 2011·Chemical Biology & Drug Design·Malakhat A TurabekovaNasrulla D Abdullaev
Aug 26, 2018·International Journal of Molecular Sciences·Jianing LiFeng Guo
Nov 11, 2008·Journal of Agricultural and Food Chemistry·Zongde WangShibin Shang

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