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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Main Authors: Snethemba S. Magwaza, Darian Naidu, Oluwatoba E. Oyeneyin, Sibusiso Senzani, Nompumelelo P. Mkhwanazi, Matshawandile Tukulula
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/10/2119
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Summary: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.
ISSN:1420-3049