Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents
HIV/AIDS and <i>Mycobacterial tuberculosis</i> (<i>Mtb</i>) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2...
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2025-05-01
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| author | Snethemba S. Magwaza Darian Naidu Oluwatoba E. Oyeneyin Sibusiso Senzani Nompumelelo P. Mkhwanazi Matshawandile Tukulula |
| author_facet | Snethemba S. Magwaza Darian Naidu Oluwatoba E. Oyeneyin Sibusiso Senzani Nompumelelo P. Mkhwanazi Matshawandile Tukulula |
| author_sort | Snethemba S. Magwaza |
| collection | DOAJ |
| description | HIV/AIDS and <i>Mycobacterial tuberculosis</i> (<i>Mtb</i>) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds <b>11g</b> (IC<sub>50</sub> = 0.388 µM), <b>11h</b> (IC<sub>50</sub> = 0.01032 µM) and <b>11i</b> (IC<sub>50</sub> = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with <b>11h</b> being 9-fold more active than AZT (IC<sub>50</sub> = 0.0909 µM), the reference drug. Furthermore, compound <b>11h</b> displayed moderate activity, with a MIC<sub>90</sub> of 88μM against <i>Mtb</i>’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for <b>11h</b>, the front runner, is >2472. Molecular docking studies revealed that <b>11h</b> interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that <b>11h</b> has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and <b>11h</b> has the potential for further optimisation as an anti-HIV-1 agent. |
| format | Article |
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| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-e9fba2ec68474e35ae4a1f4a850b14d32025-08-20T02:33:58ZengMDPI AGMolecules1420-30492025-05-013010211910.3390/molecules30102119Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV AgentsSnethemba S. Magwaza0Darian Naidu1Oluwatoba E. Oyeneyin2Sibusiso Senzani3Nompumelelo P. Mkhwanazi4Matshawandile Tukulula5School of Chemistry and Physics, University of KwaZulu Natal, Westville Campus, Durban 4001, South AfricaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban 4001, South AfricaSchool of Chemistry and Physics, University of KwaZulu Natal, Westville Campus, Durban 4001, South AfricaSchool of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban 4001, South AfricaHIV Pathogenesis Programme, Doris Duke Medical Research Institute, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban 4001, South AfricaSchool of Chemistry and Physics, University of KwaZulu Natal, Westville Campus, Durban 4001, South AfricaHIV/AIDS and <i>Mycobacterial tuberculosis</i> (<i>Mtb</i>) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds <b>11g</b> (IC<sub>50</sub> = 0.388 µM), <b>11h</b> (IC<sub>50</sub> = 0.01032 µM) and <b>11i</b> (IC<sub>50</sub> = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with <b>11h</b> being 9-fold more active than AZT (IC<sub>50</sub> = 0.0909 µM), the reference drug. Furthermore, compound <b>11h</b> displayed moderate activity, with a MIC<sub>90</sub> of 88μM against <i>Mtb</i>’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for <b>11h</b>, the front runner, is >2472. Molecular docking studies revealed that <b>11h</b> interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that <b>11h</b> has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and <b>11h</b> has the potential for further optimisation as an anti-HIV-1 agent.https://www.mdpi.com/1420-3049/30/10/2119quinoline–1,2,3-triazole–anilinesclick reactionHIV-1 subtype Bmolecular dockingDFT (density functional theory) |
| spellingShingle | Snethemba S. Magwaza Darian Naidu Oluwatoba E. Oyeneyin Sibusiso Senzani Nompumelelo P. Mkhwanazi Matshawandile Tukulula Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents Molecules quinoline–1,2,3-triazole–anilines click reaction HIV-1 subtype B molecular docking DFT (density functional theory) |
| title | Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents |
| title_full | Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents |
| title_fullStr | Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents |
| title_full_unstemmed | Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents |
| title_short | Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents |
| title_sort | synthesis characterisation biological evaluation and in silico studies of quinoline 1 2 3 triazole anilines as potential antitubercular and anti hiv agents |
| topic | quinoline–1,2,3-triazole–anilines click reaction HIV-1 subtype B molecular docking DFT (density functional theory) |
| url | https://www.mdpi.com/1420-3049/30/10/2119 |
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