Bioorganic and Medicinal Chemistry p. 5420 - 5426 (2018)
Update date:2022-08-17
Topics:
Yang, Huibin
Liu, Tian
Qi, Huitang
Huang, Zhisong
Hao, Zesheng
Ying, Junwu
Yang, Qing
Qian, Xuhong
N-acetyl-β-D-hexosaminidase (Hex) is potential target for pesticide design. Here, a series of thiazolylhydrazone derivatives were designed, synthesized and evaluated as competitive inhibitors of OfHex1, a Hex from the agricultural pest Ostrinia furnacalis. The derivative 3k, with a (benzyloxy)methyl group at the N3 atom, demonstrated greater potency with a Ki of 10.2 μM. Molecular docking analysis indicated that the (benzyloxy)methyl group of 3k was bound to a previously unexplored pocket formed by Loop478-496. Then further optimization around naphthalene ring led to find the more potency substituent phenyl. The derivative 7, with phenoxyethyl group at R1 and a phenyl group at R2, demonstrated an augmented potency with a Ki of 2.1 μM. Molecular docking analysis indicated that 7 was bound to the active pocket of OfHex1 more favorably than 3k. This work suggests a novel scaffold for developing specific Hex inhibitors.
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Doi:10.3987/COM-14-13092
(2014)Doi:10.1016/j.catcom.2019.105748
(2019)Doi:10.1039/c4nj00992d
(2015)Doi:10.1016/S0960-894X(96)00491-X
(1996)Doi:10.1016/S0960-894X(02)00556-5
(2002)Doi:10.1021/acs.jafc.9b01790
(2019)