Lavanya Kanamarlapudi Joshna, Kaur Kamalpreet, Jaitak Vikas
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Ghudda, Bathinda, Punjab, 151401, India.
Curr Comput Aided Drug Des. 2024;20(4):374-383. doi: 10.2174/1573409919666230321145543.
Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored.
Synthesis and in-silico studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds' capacity to bind ER-α protein target.
In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted.
Most of the synthesized compounds have shown dock scores ranging from -6.658 to - 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein's active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds' ADME properties are below acceptable limits.
Compound 3e showed the best docking score of -8.911. All compounds' ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro and in-vivo in the future.
乳腺癌（BC）是全球女性中仅次于肺癌的第二大癌症相关死亡原因。雌激素受体（ERs）对乳腺癌的发展有显著影响。当前癌症治疗存在选择性、靶点特异性、细胞毒性以及产生耐药性等问题。噻唑支架由于其广泛的生物活性在药物研发中越来越受欢迎。它具有控制多种细胞途径的非凡能力，其选择性抗癌活性的潜力值得探索。
合成4-苯基噻唑-2-胺衍生物作为抗乳腺癌药物并进行计算机模拟研究，利用分子对接评估化合物与ER-α蛋白靶点结合的能力。
本研究合成了4-苯基噻唑-2-胺衍生物（3a-j），并使用薛定谔软件对这些化合物进行了分子对接和药物代谢动力学（ADME）研究。
大多数合成化合物的对接分数在-6.658至-8.911千卡/摩尔之间，优于标准药物他莫昔芬（-6.821千卡/摩尔）。根据分子对接结果，所有化合物都能契合蛋白质的活性位点，并且与标准药物他莫昔芬具有相同的疏水口袋。此外，所有化合物的ADME性质均低于可接受限度。
化合物3e显示出最佳对接分数-8.911。所有化合物的ADME性质均在可接受限度内，它们的油水分配系数落在一定范围内，表明它们在作用部位都将有足够的吸收。这些化合物未来可进行体外和体内评估。
