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Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis

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Abstract

In the present work, a series of bisbenzazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Bisbenzazole derivatives showed significant antiproliferative activity against all the four tested cancer cell lines. Among the various bisbenzazole derivatives, bisbenzoxazole derivatives exhibited the most promising anticancer activity followed by bisbenzimidazole and bisbenzothiazole derivatives. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in normal human cells, indicating selective and efficient antiproliferative activity of these bisbenzazole derivatives. The structure–activity relationships of heteroaromatic systems and linkers present in bisbenzazole derivatives were analyzed in detail. In silico ADMET prediction revealed that bisbenzazole is a drug-like small molecule with a favorable safety profile. Compound 31 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from methotrexate.

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Twenty-one bisbenzoxazole derivatives have been designed synthesized and evaluated to be an antiproliferative activity against four human tumor cell lines.

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Acknowledgements

We thank the Scientific and Technological Research Council of Turkey (TUBITAK, Grant Number: 115S190) and Mersin University (Project Number: 2018-1-TP3-2911) for their financial support.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mersin University, 33169, Mersin, Turkey

    Ronak Haj Ersan & Oztekin Algul

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44280, Malatya, Turkey

    Mehmet Abdullah Alagoz

  3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560, Ankara, Turkey

    Tugba Ertan-Bolelli

  4. Department of Medical Microbiology, Medical Faculty, Mustafa Kemal University, 31100, Antakya, Hatay, Turkey

    Nizami Duran

  5. Department of Chemistry, Faculty of Science, Ataturk University, 25240, Erzurum, Turkey

    Serdar Burmaoglu

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  1. Ronak Haj Ersan
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Ersan, R.H., Alagoz, M.A., Ertan-Bolelli, T. et al. Head-to-head bisbenzazole derivatives as antiproliferative agents: design, synthesis, in vitro activity, and SAR analysis. Mol Divers 25, 2247–2259 (2021). https://doi.org/10.1007/s11030-020-10115-0

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