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Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs

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Abstract

A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a–x together with thiazoles 13 and 14 were synthesized. Compounds 7a–l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 μM with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4+ lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 ± 0.10 µM and 4.8 ± 0.08 µM against Hep-G2 cell lines, respectively.

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Acknowledgments

This work was financially supported by Higher Education Commission (HEC) of Pakistan through a Ph.D. fellowship to Mahmood-ul-Hassan Khan under “Indigenous Ph.D 5000 Fellowship Program”. Miss A. Friemel of the Chemistry Department, University of Konstanz, Germany, is highly acknowledged for the NMR experiments.

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Authors and Affiliations

  1. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Mahmood-ul-Hassan Khan, Shahid Hameed & Tashfeen Akhtar

  2. Department of Chemistry, Mirpur University of Science and Technology (MUST), Mirpur, Azad Jammu & Kashmir, Pakistan

    Tashfeen Akhtar

  3. Department of Chemistry, College of Science, University of Basrah, Basrah, Iraq

    Najim A. Al-Masoudi

  4. Department of Physiology, Pharmacology and Chemistry, College of Veterinary Medicine, University of Basrah, Basrah, Iraq

    Wasfi A. Al-Masoudi

  5. Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, Braunschweig, 38106, Germany

    Peter G. Jones

  6. Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B-3000, Belgium

    Christophe Pannecouque

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  1. Mahmood-ul-Hassan Khan
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Correspondence to Najim A. Al-Masoudi.

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Najim A. Al-Masoudi’s present address: Am Tannenhof 8, 78464 Konstanz, Germany

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Khan, MuH., Hameed, S., Akhtar, T. et al. Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs. Med Chem Res 25, 2399–2409 (2016). https://doi.org/10.1007/s00044-016-1669-9

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