Abstract

With the goal to discover a new antitumor drug with the better or similar effects to existing, a small series of β-diketonate was tested on a cisplatin-resistant MDA-MB-231 and HeLa tumor cell lines, and nontumor MRC-5 cell line. All compounds showed notable cytotoxicity against both tumor cell lines and good selectivity. Importantly, β-diketonates displayed greater selectivity than cisplatin, which is the crucial factor for a new antitumor drug candidate. Further, investigations with biomacromolecules such as DNA and serum albumin were performed. Investigations showed that tested compounds bind to DNA through intercalation and have appropriate affinity for binding to bovine serum albumin. In addition, the molecular docking study was performed to investigate more specifically the sites and binding mode of tested β-diketonate to DNA or bovine serum albumin. In conclusion, all results indicated the big potential of these compounds for application in clinical practice in future.

摘要

为了发现一种与现有药物具有更好或相似效果的新抗肿瘤药物，在顺铂耐药的 MDA-MB-231 和 HeLa 肿瘤细胞系以及非肿瘤 MRC-5 细胞系上测试了一小批β-二酮酸盐。所有化合物均对肿瘤细胞系表现出显着的细胞毒性和良好的选择性。重要的是，β-二酮酸盐表现出比顺铂更高的选择性，这是新的抗肿瘤候选药物的关键因素。此外，还进行了DNA和血清白蛋白等生物大分子的研究。研究表明，测试的化合物通过嵌入与 DNA 结合，并具有与牛血清白蛋白结合的适当亲和力。此外，还进行了分子对接研究，以更具体地研究测试的β-二酮酸与DNA或牛血清白蛋白的结合位点和结合模式。总之，所有结果都表明这些化合物在未来临床实践中应用的巨大潜力。