Başaran Eyüp, Çakmak Reşit, Sahin Dicle, Köprü Semiha, Türkmenoğlu Burçin, Akkoc Senem
Department of Chemistry and Chemical Processing Technologies, Vocational School of Technical Sciences, Batman University, Batman, Turkey.
Medical Laboratory Techniques Program, Vocational School of Health Services, Batman University, Batman, Turkey.
J Biomol Struct Dyn. 2025 May;43(8):4111-4124. doi: 10.1080/07391102.2024.2301747. Epub 2024 Jan 10.
Cancer is a global public health problem affecting millions of people every year. New anticancer drug candidates are needed to overcome the resistance to drugs used in the treatment of various types of cancer. In this study, two new series of benzenesulfonate-based thymol derivatives (- and -) were synthesized for the first time as promising chemotherapeutic agents and characterized using FT-IR, 1D NMR (H- and C-NMR, APT, DEPT 135), 2D NMR (HETCOR and HMBC), and elemental analysis (CHNS). Antiproliferative activity of the molecules was determined against cancer cell lines, namely, the human lung adenocarcinoma cell line (A549) and the colorectal adenocarcinoma cell line (DLD-1), using MTT method for both 48 and 72 h. Compounds (-) showed cytotoxic activities against A549 with IC values ranging from 9.98 to 81.83 μM, respectively, compared to cisplatin (6.65 μM). These compounds exhibited antiproliferative activities against DLD-1 cancer cells at concentrations ranging from 4.29 to 53.62 μM, respectively, compared to cisplatin (9.91 μM). Especially, compound displayed significant cytotoxicity on A549 and DLD-1 cancer cells with IC values of 9.98 and 10.75 μM, respectively. Finally, molecular docking studies were performed with Bcl-2, VEGFR-2, EGFR, and HER2 targets using the Schrödinger 2021-2 Maestro Glide program. The binding energy values and binding interactions of compounds and were determined to be the result of their interactions with these targets. Schrödinger 2021-2 Qikprop wizard drug similarity ratios and ADME prediction of all compounds were also calculated.
癌症是一个全球性的公共卫生问题，每年影响着数百万人。需要新的抗癌药物候选物来克服对用于治疗各种类型癌症的药物的耐药性。在本研究中，首次合成了两个新的基于苯磺酸盐的百里酚衍生物系列（- 和 -）作为有前景的化疗药物，并使用傅里叶变换红外光谱（FT-IR）、一维核磁共振（氢谱和碳谱、APT、DEPT 135）、二维核磁共振（HETCOR和HMBC）以及元素分析（CHNS）对其进行了表征。使用MTT法在48小时和72小时对这些分子针对癌细胞系，即人肺腺癌细胞系（A549）和结肠直肠腺癌细胞系（DLD-1）的抗增殖活性进行了测定。与顺铂（6.65 μM）相比，化合物（-）对A549显示出细胞毒性活性，IC值分别在9.98至81.83 μM范围内。这些化合物对DLD-1癌细胞的抗增殖活性浓度分别在4.29至53.62 μM范围内，与顺铂（9.91 μM）相比。特别是，化合物 对A549和DLD-1癌细胞表现出显著的细胞毒性，IC值分别为9.98和10.75 μM。最后，使用Schrödinger 2021-2 Maestro Glide程序对Bcl-2、VEGFR-2、EGFR和HER2靶点进行了分子对接研究。确定了化合物 和 的结合能值以及结合相互作用是它们与这些靶点相互作用的结果。还计算了Schrödinger 2021-2 Qikprop向导的所有化合物 的药物相似性比率和ADME预测。
