开发一种物种选择性乙酰胆碱酯酶抑制剂以控制疟疾的蚊媒冈比亚按蚊。
Towards a species-selective acetylcholinesterase inhibitor to control the mosquito vector of malaria, Anopheles gambiae.
作者信息
Carlier Paul R, Anderson Troy D, Wong Dawn M, Hsu Danny C, Hartsel Joshua, Ma Ming, Wong Eric A, Choudhury Ranginee, Lam Polo C-H, Totrov Maxim M, Bloomquist Jeffrey R
机构信息
Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA.
出版信息
Chem Biol Interact. 2008 Sep 25;175(1-3):368-75. doi: 10.1016/j.cbi.2008.04.037. Epub 2008 May 4.
Anopheles gambiae is the major mosquito vector of malaria in sub-Saharan Africa. At present, insecticide-treated nets (ITNs) impregnated with pyrethroid insecticides are widely used in malaria-endemic regions to reduce infection; however the emergence of pyrethroid-resistant mosquitoes has significantly reduced the effectiveness of the pyrethroid ITNs. An acetylcholinesterase (AChE) inhibitor that is potent for An. gambiae but weakly potent for the human enzyme could potentially be safely deployed on a new class of ITNs. In this paper we provide a preliminary pharmacological characterization of An. gambiae AChE, discuss structural features of An. gambiae and human AChE that could lead to selective inhibition, and describe compounds with 130-fold selectivity for inhibition of An. gambiae AChE relative to human AChE.
冈比亚按蚊是撒哈拉以南非洲地区疟疾的主要蚊虫传播媒介。目前，浸渍拟除虫菊酯类杀虫剂的经杀虫剂处理的蚊帐（ITNs）在疟疾流行地区被广泛用于减少感染；然而，拟除虫菊酯抗性蚊子的出现显著降低了拟除虫菊酯ITNs的有效性。一种对冈比亚按蚊有强效但对人类酶效力较弱的乙酰胆碱酯酶（AChE）抑制剂可能有望安全地应用于新型ITNs。在本文中，我们提供了冈比亚按蚊AChE的初步药理学特征，讨论了冈比亚按蚊和人类AChE可能导致选择性抑制的结构特征，并描述了对冈比亚按蚊AChE相对于人类AChE具有130倍选择性抑制作用的化合物。
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