Zhang Yiying, Wang Rao, Bu Yueyue, Corona Angela, Dettori Laura, Tramontano Enzo, Pannecouque Christophe, De Clercq Erik, Wang Shuai, Meng Ge, Chen Fen-Er
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.
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.
靶向核糖核酸酶H（RNase H）已成为治疗HIV-1极具前景的策略。在本研究中，设计并合成了一系列新型3-肼基吲哚-2-酮衍生物作为HIV-1 RNase H的潜在抑制剂。值得注意的是，其中几种衍生物表现出微摩尔级的抑制活性。在所研究的化合物中，命中化合物对HIV-1 RNase H表现出强效抑制作用，其Ki值为2.31 μM。此外，这种一般结构中最有效的化合物表现出显著的抑制活性，Ki值为0.55 μM。通过对接研究，揭示了该配体在RNase H活性位点内的关键相互作用。这种新型化学结构可被视为未来开发RNase H抑制剂的潜在骨架。
