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N-(5-acetyl-4-methylthiazol-2-yl)arylamide derivatives as multi-target-directed ligands: design, synthesis, biochemical evaluation and computational analysis

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Abstract

In the present study, we are reporting the synthesis of a total eight derivatives of N-(5-acetyl-4-methylthiazol-2-yl) Arylamide derivatives (3a-h). The products obtained in good to excellent yield represents drug-like molecules with a well-developed structure-activity relationship. All the synthesized compounds were further subjected to chemical characterization (NMR, FTIR and elemental analysis) and further tested for biological activities (antioxidant, antibacterial, antifungal and α-glucosidase). The anti-oxidant properties of compound 3h (IC50 ± SEM = 141.9 ± 1.12 µg/mL) were found maximum in comparison to the rest of the derivatives. The antibacterial results showed the compounds 3d and 3h as a significant bacterial inhibitor. The significant fungicidal activity was observed by compound 3a with the zone of inhibition up to 24 mm which in comparison with the results of positive control (Terbinafine). When the effect was observed on α-glucosidase activity, the highest enzyme inhibition activity was observed by 3h (IC50 ± SEM 134.4 ± 1.01 µg/mL) followed by 3c (IC50 ± SEM = 157.3 ± 1.11 µg/mL). The results were further supported by molecular docking studies and the chemical stability of the derivatives was also performed by density functional theory (DFTs) calculations. The data revealed that most of the derivatives are multi-target ligands and can be used as lead molecules for the synthesis of derivatives for their further evaluation at molecular targets for the treatment of specific diseases.

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Synopsis This article reports the synthesis of a total of eight derivatives of N-(5-acetyl-4-methylthiazol-2-yl) Arylamide derivatives. The products obtained in good to excellent yield represents drug-like molecules with a well-developed structure-activity relationship.

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Acknowledgement

The author Syeda Abida Ejaz is grateful to the Offices of Research, Innovation and Commercialization (ORIC), The Islamia University of Bahawalpur, Pakistan for the financial support through Project No. 3890/ORIC/IUB/2021.

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Author notes

  1. † These authors contributed equally to this work.

Authors and Affiliations

  1. Dr. M A Kazi Institute of Chemistry, University of Sindh, Jamshoro, 76080, Pakistan

    Rabail Ujan

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    Hafiz Mohammad Kashif Mahmood, Syeda Abida Ejaz & Amna Saeed

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

    Pervaiz Ali Channar, Shomaila Saeed, Aamer Saeed & Mamoona Rafiq

  4. Department of Oral and Maxillofacial Surgery, Institute of Dentistry, Liaquat University, Jamshoro, 76080, Pakistan

    Kashif Ali Channar

  5. National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080, Pakistan

    Hafiz Abdul Bari Indher

  6. Department of Biochemistry and Biotechnology, University of Gujrat, Gujrat, 50700, Pakistan

    Hammad Ismail

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  1. Rabail Ujan
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  2. Hafiz Mohammad Kashif Mahmood
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Correspondence to Syeda Abida Ejaz or Aamer Saeed.

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Ujan, R., Mahmood, H.M.K., Channar, P.A. et al. N-(5-acetyl-4-methylthiazol-2-yl)arylamide derivatives as multi-target-directed ligands: design, synthesis, biochemical evaluation and computational analysis. J Chem Sci 134, 7 (2022). https://doi.org/10.1007/s12039-021-01998-z

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  • DOI: https://doi.org/10.1007/s12039-021-01998-z

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