VNX-000440系列均三嗪类杀虫活性物质的发现和活性

ω-hexatoxin-Hv1a是蜘蛛体内存在的多肽毒素,是昆虫电压门控离子通道拮抗剂。建立了此物质的3D药效团模型,用计算机从已知的商品化物质数据库中筛选出了与药效团模型相匹配的物质,并进一步用Accelrys软件进行筛选。对选出的物质进行活性测定,均三嗪类物质VNX-000440是得到的一个活性物质。经结构修饰得到了对埃及伊蚊和甜菜夜蛾活性高的物质VNX-000443。经对蜚蠊DUM神经元离子通道的影响测定试验,发现此类物质对昆虫电压门控离子通道有抑制作用。

Discover and Activity of VNX-000440 Series of Triazine Insecticides

ω-hexatoxin-Hv1a is a peptide neurotoxin of spiders, an antagonist of insect voltage-gated calcium channels. First build 3D pharmacophore models of ω-hexatoxin-Hv1a, then search compounds matching the chemical features of the pharmacophore from Accelrys Chemicals Available for Purchasing database. After further screen with Accelrys software and bioactivity assay, VNX-000440 is found. Based on the modification to the structure of VNX-000440, a high activity compound against S. exigua and A. aegypti ,VNX-000443 is discovered. The experiment about the effects of VNX-000440 series compounds on the ion channels of DUM neurons shows that these substances have inhibition on the insect voltage-gated ion channels.