Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors
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 i...
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| Format: | Article |
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MDPI AG
2025-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/9/1868 |
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| author | Yiying Zhang Rao Wang Yueyue Bu Angela Corona Laura Dettori Enzo Tramontano Christophe Pannecouque Erik De Clercq Shuai Wang Ge Meng Fen-Er Chen |
| author_facet | Yiying Zhang Rao Wang Yueyue Bu Angela Corona Laura Dettori Enzo Tramontano Christophe Pannecouque Erik De Clercq Shuai Wang Ge Meng Fen-Er Chen |
| author_sort | Yiying Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-794c26eeb861458297a09db23b8a8f3e |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-794c26eeb861458297a09db23b8a8f3e2025-08-20T03:52:58ZengMDPI AGMolecules1420-30492025-04-01309186810.3390/molecules30091868Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H InhibitorsYiying Zhang0Rao Wang1Yueyue Bu2Angela Corona3Laura Dettori4Enzo Tramontano5Christophe Pannecouque6Erik De Clercq7Shuai Wang8Ge Meng9Fen-Er Chen10Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, ChinaHenan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaHenan Key Laboratory of Nanomedicine for Targeting Diagnosis and Treatment, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaDepartment of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, ItalyDepartment of Life and Environmental Sciences, University of Cagliari, 09042 Monserrato, ItalyRega Institute for Meical Research, KU Leuven, Herestraat 49, B-3000 Leuven, BelgiumRega Institute for Meical Research, KU Leuven, Herestraat 49, B-3000 Leuven, BelgiumEngineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, ChinaEngineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, ChinaEngineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, ChinaTargeting 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.https://www.mdpi.com/1420-3049/30/9/1868AIDSHIV3-hydrazonoindolin-2-oneRNase H |
| spellingShingle | Yiying Zhang Rao Wang Yueyue Bu Angela Corona Laura Dettori Enzo Tramontano Christophe Pannecouque Erik De Clercq Shuai Wang Ge Meng Fen-Er Chen Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors Molecules AIDS HIV 3-hydrazonoindolin-2-one RNase H |
| title | Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors |
| title_full | Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors |
| title_fullStr | Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors |
| title_full_unstemmed | Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors |
| title_short | Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors |
| title_sort | design synthesis and biological evaluation of 3 hydrazonoindolin 2 one derivatives as novel hiv 1 rnase h inhibitors |
| topic | AIDS HIV 3-hydrazonoindolin-2-one RNase H |
| url | https://www.mdpi.com/1420-3049/30/9/1868 |
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