Huang Leilei, Huang Jinwen, Nie Hui, Li Yingzi, Song Lixing, Wu Fanhong
Department of Pharmaceutical Engineering, School of Chemical and Environmental Engineering, Shanghai Institute of Technology Shanghai China
Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology China.
RSC Med Chem. 2021 Jun 23;12(8):1374-1380. doi: 10.1039/d0md00372g. eCollection 2021 Aug 18.
A series of combretastatin A-4 (CA-4) sulfamate derivatives were synthesized and their structure-activity relationship on tubulin, arylsulfatase and tumor cell antiproliferation inhibition was studied. Among them, compound showed excellent potency as well as CA-4 under the same conditions against six tumor cells including HTC-116, HeLa, HepG2, MGC803, MKN45 and MCF-7 cells, respectively. Molecular docking revealed that several important hydrogen bond interactions were formed between the sulfamate group of and the colchicine binding site of tubulin and steroid sulfatase respectively. Although compound was less active than CA-4 in regard to its activity as an inhibitor of tubulin polymerization, it was effective as an inhibitor of arylsulfatase. This novel combretastatin A-4 sulfamate derivative has the potential to be developed as a dual inhibitor of tubulin polymerization and arylsulfatase for cancer therapy.
合成了一系列柯里拉京A - 4（CA - 4）氨基磺酸盐衍生物，并研究了它们在微管蛋白、芳基硫酸酯酶和肿瘤细胞抗增殖抑制方面的构效关系。其中，化合物在相同条件下分别对包括HTC - 116、HeLa、HepG2、MGC803、MKN45和MCF - 7细胞在内的六种肿瘤细胞表现出与CA - 4相当的优异活性。分子对接显示，该化合物的氨基磺酸酯基团分别与微管蛋白的秋水仙碱结合位点和类固醇硫酸酯酶形成了几个重要的氢键相互作用。虽然该化合物作为微管蛋白聚合抑制剂的活性比CA - 4低，但它作为芳基硫酸酯酶抑制剂是有效的。这种新型的柯里拉京A - 4氨基磺酸盐衍生物有潜力被开发为用于癌症治疗的微管蛋白聚合和芳基硫酸酯酶的双重抑制剂。
