Department of Pharmacy, The First Afflicted Hospital of Chengdu Medical College, No. 278, Baoguang Rd, Xindu Region, Chengdu, 610500, People's Republic of China.
School of Life Science and Engineering, Southwest Jiaotong University, No. 111, Erhuan Rd, Chengdu, 610031, People's Republic of China.
Sci Rep. 2022 Jun 15;12(1):10021. doi: 10.1038/s41598-022-14172-3.
A series of new paclitaxel-benzoxazoles hybrids were designed based on both the molecular docking mode of beta-tubulin with paclitaxel derivatives (7a and 7g), and the activity-structure relationship of C-13 side chain in paclitaxel. Palladium-catalyzed direct Csp-H arylation of benzoxazoles with different aryl-bromides was used as the key synthetic strategy for the aryl-benzoxazoles moieties in the hybrids. Twenty-six newly synthesized hybrids were screened for their antiproliferative activity against human cancer cell lines such as human breast cancer cells (MDA-MB-231) and liver hepatocellular cells (HepG2) by the MTT assay and results were compared with paclitaxel. Interestingly, most hybrids (7a-7e, 7i, 7k, 7l, 7A, 7B, 7D and 7E) showed significantly active against both cell lines at concentration of 50 µM, which indicated that the hybrid strategy is effective to get structural simplified paclitaxel analogues with high anti-tumor activity.
基于β-微管蛋白与紫杉醇衍生物（7a 和 7g）的分子对接模式以及紫杉醇 C-13 侧链的活性-结构关系，设计了一系列新型紫杉醇-苯并恶唑类杂合物。钯催化的苯并恶唑与不同芳基溴化物的直接 Csp-H 芳基化反应被用作杂合物中芳基苯并恶唑部分的关键合成策略。通过 MTT 法筛选了 26 种新合成的杂合物对人乳腺癌细胞（MDA-MB-231）和肝癌细胞（HepG2）等人类癌细胞系的增殖活性，并与紫杉醇进行了比较。有趣的是，大多数杂合物（7a-7e、7i、7k、7l、7A、7B、7D 和 7E）在 50µM 浓度下对两种细胞系均表现出显著的活性，这表明杂合策略对于获得具有高抗肿瘤活性的结构简化的紫杉醇类似物是有效的。
