Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors
Yiying Zhang,
Rao Wang,
Yueyue Bu,
Angela Corona,
Laura Dettori,
Enzo Tramontano,
Christophe Pannecouque,
Erik De Clercq,
Shuai Wang,
Ge Meng,
Fen-Er Chen
Affiliations
Yiying Zhang
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China
Rao Wang
Henan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
Yueyue Bu
Henan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
Angela Corona
Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Italy
Laura Dettori
Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Italy
Enzo Tramontano
Department of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, Italy
Christophe Pannecouque
Rega Institute for Meical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Erik De Clercq
Rega Institute for Meical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Shuai Wang
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China
Ge Meng
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China
Fen-Er Chen
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China
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.
