540519-16-2Relevant academic research and scientific papers
Pocket-based Lead Optimization Strategy for the Design and Synthesis of Chitinase Inhibitors
Dong, Yawen,Hu, Song,Jiang, Xi,Liu, Tian,Ling, Yun,He, Xiongkui,Yang, Qing,Zhang, Li
, p. 3575 - 3582 (2019)
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.
