Natacha Mérindol , Seyedeh Mahsa Hashemian , Seynabou Sokhna , Marie-Pierre Girard , Marc Presset , Insa Seck , Lalla Aïcha Ba , Seydou Ka , Samba Fama Ndoye , Issa Samb , Erwan Le Gall , Lionel Berthoux , Matar Seck , Isabel Desgagné-Penix
{"title":"三氮杂烯作为HIV-1和HCoV-OC43抑制剂的构效关系研究","authors":"Natacha Mérindol , Seyedeh Mahsa Hashemian , Seynabou Sokhna , Marie-Pierre Girard , Marc Presset , Insa Seck , Lalla Aïcha Ba , Seydou Ka , Samba Fama Ndoye , Issa Samb , Erwan Le Gall , Lionel Berthoux , Matar Seck , Isabel Desgagné-Penix","doi":"10.1016/j.ejmcr.2025.100288","DOIUrl":null,"url":null,"abstract":"<div><div>Triazenes, or amino-substituted diazenes, are organic compounds containing three contiguous nitrogen atoms, that have potent biological activities. We previously demonstrated that triazenes, particularly those substituted with a phenyl or 3-pyridyl ring at the 1-position and a 2-pyridyl ring at the 3-position, exhibit anti-DENV properties. Here, we evaluated the antiviral activity against a betacoronavirus (HCoV-OC43) and a lentivirus (HIV-1). 1-(4-trifluoromethylphenyl)-2-imidazole-1-yldiazene (<strong>21</strong>) exhibited broad-spectrum activity (EC<sub>50</sub> = 6.6–6.8 μM) but was cytotoxic to THP-1 cells. Pyridyl triazenes (<strong>14, 15</strong>) were the most potent against HCoV-OC43, while 1-(4-methoxyphenyl)-2-morpholin-4-yldiazene (<strong>6</strong>) and 1-(4-methoxyphenyl)3-(-6-methylpyridin-2-yl)triazene (<strong>10</strong>) inhibited HIV-1 the most. Structure–activity relationship analysis, supported by molecular docking, indicated that <em>para</em>-methoxy groups favored interactions with viral enzyme binding pockets, enhancing antiviral potency, while <em>meta</em> and <em>para</em>-trifluoromethyl groups were associated with reduced activity and increased cytotoxicity. These findings support the further development of triazenes as antiviral scaffolds.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100288"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Triazenes as inhibitors of HIV-1 and HCoV-OC43: A structure-activity relationship study\",\"authors\":\"Natacha Mérindol , Seyedeh Mahsa Hashemian , Seynabou Sokhna , Marie-Pierre Girard , Marc Presset , Insa Seck , Lalla Aïcha Ba , Seydou Ka , Samba Fama Ndoye , Issa Samb , Erwan Le Gall , Lionel Berthoux , Matar Seck , Isabel Desgagné-Penix\",\"doi\":\"10.1016/j.ejmcr.2025.100288\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Triazenes, or amino-substituted diazenes, are organic compounds containing three contiguous nitrogen atoms, that have potent biological activities. We previously demonstrated that triazenes, particularly those substituted with a phenyl or 3-pyridyl ring at the 1-position and a 2-pyridyl ring at the 3-position, exhibit anti-DENV properties. Here, we evaluated the antiviral activity against a betacoronavirus (HCoV-OC43) and a lentivirus (HIV-1). 1-(4-trifluoromethylphenyl)-2-imidazole-1-yldiazene (<strong>21</strong>) exhibited broad-spectrum activity (EC<sub>50</sub> = 6.6–6.8 μM) but was cytotoxic to THP-1 cells. Pyridyl triazenes (<strong>14, 15</strong>) were the most potent against HCoV-OC43, while 1-(4-methoxyphenyl)-2-morpholin-4-yldiazene (<strong>6</strong>) and 1-(4-methoxyphenyl)3-(-6-methylpyridin-2-yl)triazene (<strong>10</strong>) inhibited HIV-1 the most. Structure–activity relationship analysis, supported by molecular docking, indicated that <em>para</em>-methoxy groups favored interactions with viral enzyme binding pockets, enhancing antiviral potency, while <em>meta</em> and <em>para</em>-trifluoromethyl groups were associated with reduced activity and increased cytotoxicity. These findings support the further development of triazenes as antiviral scaffolds.</div></div>\",\"PeriodicalId\":12015,\"journal\":{\"name\":\"European Journal of Medicinal Chemistry Reports\",\"volume\":\"15 \",\"pages\":\"Article 100288\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medicinal Chemistry Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2772417425000445\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772417425000445","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Triazenes as inhibitors of HIV-1 and HCoV-OC43: A structure-activity relationship study
Triazenes, or amino-substituted diazenes, are organic compounds containing three contiguous nitrogen atoms, that have potent biological activities. We previously demonstrated that triazenes, particularly those substituted with a phenyl or 3-pyridyl ring at the 1-position and a 2-pyridyl ring at the 3-position, exhibit anti-DENV properties. Here, we evaluated the antiviral activity against a betacoronavirus (HCoV-OC43) and a lentivirus (HIV-1). 1-(4-trifluoromethylphenyl)-2-imidazole-1-yldiazene (21) exhibited broad-spectrum activity (EC50 = 6.6–6.8 μM) but was cytotoxic to THP-1 cells. Pyridyl triazenes (14, 15) were the most potent against HCoV-OC43, while 1-(4-methoxyphenyl)-2-morpholin-4-yldiazene (6) and 1-(4-methoxyphenyl)3-(-6-methylpyridin-2-yl)triazene (10) inhibited HIV-1 the most. Structure–activity relationship analysis, supported by molecular docking, indicated that para-methoxy groups favored interactions with viral enzyme binding pockets, enhancing antiviral potency, while meta and para-trifluoromethyl groups were associated with reduced activity and increased cytotoxicity. These findings support the further development of triazenes as antiviral scaffolds.