新型HIV-1核糖核酸酶H抑制剂3-肼基吲哚-2-酮衍生物的设计、合成及生物学评价

Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors.

作者信息

Zhang Yiying, Wang Rao, Bu Yueyue, Corona Angela, Dettori Laura, Tramontano Enzo, Pannecouque Christophe, De Clercq Erik, Wang Shuai, Meng Ge, Chen Fen-Er

机构信息

Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China.

Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, China.

出版信息

Molecules. 2025 Apr 22;30(9):1868. doi: 10.3390/molecules30091868.

Targeting ribonuclease H (RNase H) has emerged as a highly promising strategy for treating HIV-1. In this study, a series of novel 3-hydrazonoindolin-2-one derivatives were designed and synthesized as potential inhibitors of HIV-1 RNase H. Notably, several of these derivatives displayed micromolar inhibitory activity. Among the compounds examined, the hit compound demonstrated potent inhibition of HIV-1 RNase H, boasting a Ki value of 2.31 μM. Additionally, the most potent compound of this general structure exhibited remarkable inhibitory activity, with Ki values of 0.55 μM. Through docking studies, the key interactions of this ligand within the active site of RNase H were uncovered. This novel chemical structure can be regarded as a prospective scaffold for the future development of RNase H inhibitors.