5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action.
| Autor: | Corona A; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Meleddu R; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Delelis O; Laboratory of Biology and Applied Pharmacology (LBPA), Ecole Normale Supérieure (ENS) Cachan, Centre National de la Recherche Scientifique (CNRS), Cachan, France., Subra F; Laboratory of Biology and Applied Pharmacology (LBPA), Ecole Normale Supérieure (ENS) Cachan, Centre National de la Recherche Scientifique (CNRS), Cachan, France., Cottiglia F; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Esposito F; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Distinto S; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Maccioni E; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy., Tramontano E; Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Jun 23; Vol. 13, pp. 1193280. Date of Electronic Publication: 2023 Jun 23 (Print Publication: 2023). |
| DOI: | 10.3389/fcimb.2023.1193280 |
| Abstrakt: | In the effort to identify and develop new HIV-1 inhibitors endowed with innovative mechanisms, we focused our attention on the possibility to target more than one viral encoded enzymatic function with a single molecule. In this respect, we have previously identified by virtual screening a new indolinone-based scaffold for dual allosteric inhibitors targeting both reverse transcriptase-associated functions: polymerase and RNase H. Pursuing with the structural optimization of these dual inhibitors, we synthesized a series of 35 new 3-[2-(4-aryl-1,3-thiazol-2-ylidene)hydrazin-1-ylidene]1-indol-2-one and 3-[3-methyl-4-arylthiazol-2-ylidene)hydrazine-1-ylidene)indolin-2-one derivatives, which maintain their dual inhibitory activity in the low micromolar range. Interestingly, compounds 1a, 3a, 10a, and 9b are able to block HIV-1 replication with EC Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Corona, Meleddu, Delelis, Subra, Cottiglia, Esposito, Distinto, Maccioni and Tramontano.) |
| Databáze: | MEDLINE |
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