几丁质酶
铅化合物
铅(地质)
化学
生物化学
生化工程
酶
生物技术
计算生物学
计算机科学
组合化学
生物
工程类
体外
古生物学
作者
Yawen Dong,Song Hu,Xi Jiang,Tian Liu,Yun Ling,Xiongkui He,Qing Yang,Li Zhang
标识
DOI:10.1021/acs.jafc.9b00837
摘要
Insect chitinases play an indispensable role in shedding old cuticle during molting. Targeting chitinase inhibition is a promising pest control strategy. Of ChtI, a chitinase from the destructive insect pest Ostrinia furnacalis (Asian corn borer), has been suggested as a potential target for designing green pesticides. A 4,5,6,7-tetrahydrobenzo[ b]thiophene-3-carboxylate scaffold was previously obtained, and further derivatization generated the lead compound 1 as Of ChtI inhibitor. Here, based on the predicted binding mode of compound 1, the pocket-based lead optimization strategy was applied. A series of analogues was synthesized, and their inhibitory activities against Of ChtI were evaluated. Compound 8 with 6- tert-pentyl showed preferential inhibitory activity with a Ki value of 0.71 μM. Their structure-activity relationships suggested that the compound with larger steric hindrance at the 6-nonpolar group was essential for inhibitory activity due to its stronger interactions with surrounding amino acids. This work provides a strategy for designing potential chitinase inhibitors.
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