Rajic Zrinka, Butula Ivan, Zorc Branka, Kraljevic Pavelic Sandra, Hock Karlo, Pavelic Kresimir, Naesens Lieve, De Clercq Erik, Balzarini Jan, Przyborowska Monika, Ossowski Tadeusz, Mintas Mladen
Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb, Croatia.
Chem Biol Drug Des. 2009 Mar;73(3):328-38. doi: 10.1111/j.1747-0285.2009.00774.x.
Non-steroidal anti-inflammatory drugs (NSAID) pharmacophores are interesting in designing potential anticancer drugs. Indeed, numerous experimental, epidemiologic and clinical studies suggest that NSAIDs are promising anticancer drugs. Herein, NSAID hydroxamic acids 3a-i were prepared by a new synthetic procedure and evaluated for their antiviral and cytostatic activity against malignant tumor cell lines and normal human fibroblasts (WI38). Antiviral activity evaluation results indicated that 3f had only a minor activity against the influenza virus A/H1N1 subtype with a selectivity index of 7-10. On the other hand, the results of the in vitro cytostatic activity evaluations revealed that the majority of NSAID hydroxamic acid derivatives 3a-i exhibited a strong non-specific antiproliferative effect at the highest concentration (100 microM) on the tested cell line panel. Only compounds 3b, 3e and 3i exerted a differential dose-dependent inhibitory activity against the growth of HeLa cells (p < 0.05) at concentration 10 microM. Among those three compounds, only compound 3b showed a selective cytostatic effect on HeLa in comparison with normal fibroblasts.
非甾体抗炎药（NSAID）药效基团在设计潜在抗癌药物方面具有重要意义。事实上，大量实验、流行病学和临床研究表明，NSAIDs是很有前景的抗癌药物。在此，通过一种新的合成方法制备了NSAID异羟肟酸3a-i，并评估了它们对恶性肿瘤细胞系和正常人成纤维细胞（WI38）的抗病毒和细胞生长抑制活性。抗病毒活性评估结果表明，3f对甲型H1N1流感病毒亚型仅具有轻微活性，选择性指数为7-10。另一方面，体外细胞生长抑制活性评估结果显示，大多数NSAID异羟肟酸衍生物3a-i在最高浓度（100 microM）时对测试细胞系显示出强烈的非特异性抗增殖作用。只有化合物3b、3e和3i在浓度为10 microM时对HeLa细胞的生长表现出不同的剂量依赖性抑制活性（p < 0.05）。在这三种化合物中，与正常成纤维细胞相比，只有化合物3b对HeLa细胞表现出选择性细胞生长抑制作用。
