A Potential Lead for Insect Growth Regulator: Design, Synthesis, and Biological Activity Evaluation of Novel Hexacyclic Pyrazolamide Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 May 13

PMID 37175151

Authors

Bingbo Guo

Biaobiao Jiang

Chunying Wang

Xiaoyu Jin

Liuyang Wang

Zhaokai Yang

Shihui Luo

Qing Yang

Li Zhang

XinLing Yang

Affiliations

Soon will be listed here.

Abstract

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound acting simultaneously on EcR and chitinase (ChtI). Their insecticidal activities against , , and larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, , exhibited promising insecticidal activities against and . Further protein binding assays and molecular docking indicated that could target both EcR and ChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.

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