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设计、合成及新型诺氟沙星类似物作为高效抗癌和抗氧化剂的评价。

Design, synthesis and evaluation of novel norfloxacin analogs as potent anticancer and antioxidant agents.

机构信息

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.

Institute of Pharmaceutical Sciences, Peoples University of Medical & Health Sciences for Women, Nawabshah - Shaheed Benazirabad, Sindh, 67480, Pakistan.

出版信息

Future Med Chem. 2024;16(17):1777-1789. doi: 10.1080/17568919.2024.2383165. Epub 2024 Aug 8.

Abstract

To synthesize a novel series of norfloxacin analogs and to evaluate biological activity. Novel norfloxacin analogs were synthesized and characterized by NMR and mass spectrometry. Antiproliferative and antioxidant properties were studied. Compound was the most potent against HeLa cell-line with 100% inhibition of cell viability IC = 3.1 ± 0.2 μM. All compounds exhibit moderate to excellent antioxidant properties. Docking study demonstrates higher binding affinity of compounds with respective anticancer (B-cell lymphoma-2) and (tyrosinase) antioxidant targets. absorption, distribution, metabolism and excretion profile of compounds proves all synthesized compounds follow Lipinski's rule of drug likeness, non toxic and possess passive gastrointestinal absorption. The biological profile suggest that the synthesized norfloxacin analogs can be a novel scaffold for future anticancer drug development.

摘要

合成了一系列新型诺氟沙星类似物,并评价了它们的生物活性。通过核磁共振波谱和质谱对新型诺氟沙星类似物进行了结构确证。研究了它们的抗增殖和抗氧化活性。化合物 对 HeLa 细胞系的抑制活性最强,细胞活力抑制率为 100%,IC = 3.1 ± 0.2 μM。所有化合物均表现出中等至良好的抗氧化活性。对接研究表明,与相应的抗癌(B 细胞淋巴瘤-2)和(酪氨酸酶)抗氧化靶点相比,化合物具有更高的结合亲和力。化合物的吸收、分布、代谢和排泄特征表明,所有合成的化合物均符合药物类似物的利宾斯基规则,无毒性,且具有被动胃肠道吸收特性。生物特征表明,所合成的诺氟沙星类似物可能成为未来抗癌药物开发的新骨架。

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