Omar Mai H, Emam Soha H, Mikhail Demiana S, Elmeligie Salwa
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Bioorg Chem. 2024 Dec;153:107930. doi: 10.1016/j.bioorg.2024.107930. Epub 2024 Oct 29.
The current review discusses the importance of combretastatin A-4 (CA-4) as a lead compound of microtubule targeting agents. CA-4 holds a unique place among naturally occurring compounds having cytotoxic activity. In this review an overall picture of design strategies, structure-activity relationship, synthesis, cytotoxic activity, and binding interactions of promising CA-4 analogues, are discussed and arranged chronologically from 2016 to early 2023. Also, this review emphasizes their biological activity as anticancer agents, within an overview of clinical application limitation and suggested strategies to overcome. Dual targeting tubulin inhibitors showed highpotentialto surpass medication resistance and provide synergistic efficacy. Linking platinum (IV), amino acids, and HDAC targeting moieties to active tubulin inhibitorsproduced potent active compounds. Analogues of CA-4 bridged with azetidin-2-one, pyrazole, sulfide, or carrying selenium atom exhibited cytotoxic action against a variety of malignant cell lines through different pathways.
本综述讨论了康普瑞汀A-4（CA-4）作为微管靶向剂先导化合物的重要性。CA-4在具有细胞毒性活性的天然化合物中占有独特地位。在本综述中，从2016年到2023年初，按时间顺序讨论并梳理了有前景的CA-4类似物的设计策略、构效关系、合成、细胞毒性活性及结合相互作用。此外，本综述在概述临床应用局限性及提出克服策略的背景下，强调了它们作为抗癌药物的生物活性。双靶点微管蛋白抑制剂显示出克服耐药性并提供协同疗效的巨大潜力。将铂（IV）、氨基酸和靶向组蛋白去乙酰化酶的部分与活性微管蛋白抑制剂相连产生了强效活性化合物。与氮杂环丁烷-2-酮、吡唑、硫化物桥连或携带硒原子的CA-4类似物通过不同途径对多种恶性细胞系表现出细胞毒性作用。
