Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Eur J Pharmacol. 2018 Aug 5;832:11-24. doi: 10.1016/j.ejphar.2018.05.011. Epub 2018 May 23.
Cancer is the second leading cause of mortality worldwide. Therapeutic approach to cancer is a multi-faceted one, whereby many cellular/enzymatic pathways have been discovered as important drug targets for the treatment of cancer. A major disadvantage of most of the currently available anticancer drugs is their non-selective cytotoxicity towards cancerous as well as healthy cells. Another major hurdle in cancer therapy is the development of resistance to anticancer drugs. This necessitates the discovery of new molecules with potent and selective cytotoxic activity towards only cancerous cells, with minimum or no damage to the normal/healthy cells. Herein we report detailed investigation into the anticancer activity of sulfamoyl benz(sulfon)amides (1a-1g, 2a-2k) and 1H-pyrazol-4-yl benzamides (3a-3j) against three cancer cell lines, breast cancer cells (MCF-7), bone-marrow cancer cells (K-562) and cervical cancer cells (HeLa). For comparison, screening against healthy baby hamster kidney cells (BHK-21) was carried out. All compounds exhibited selective cytotoxicity towards cancerous cells. Cell cycle analysis was carried out using flow cytometry, followed by fluorescence microscopic analysis. DNA interaction and docking studies were also carried out.
癌症是全球第二大死亡原因。癌症的治疗方法是多方面的,许多细胞/酶途径已被发现是治疗癌症的重要药物靶点。大多数现有抗癌药物的主要缺点是它们对癌细胞和健康细胞都具有非选择性细胞毒性。癌症治疗的另一个主要障碍是对抗癌药物产生耐药性。这就需要发现新的分子,这些分子对癌细胞具有强大而选择性的细胞毒性,对正常/健康细胞的损伤最小或没有。在此,我们详细研究了磺胺基苯(磺酰胺)(1a-1g、2a-2k)和 1H-吡唑-4-基苯甲酰胺(3a-3j)对三种癌细胞系(乳腺癌细胞 MCF-7、骨髓癌细胞 K-562 和宫颈癌细胞 HeLa)的抗癌活性。为了进行比较,还对健康的仓鼠肾细胞(BHK-21)进行了筛选。所有化合物均表现出对癌细胞的选择性细胞毒性。采用流式细胞术进行细胞周期分析,然后进行荧光显微镜分析。还进行了 DNA 相互作用和对接研究。