Department of Chemistry, Kakatiya University, Warangal-506009, Telangana State, India.
College of Chemical Engineering, Huaqiao University, Xiamen 361021, P.R. China.
Curr Med Chem. 2022;29(21):3748-3773. doi: 10.2174/0929867328666211202101641.
Although significant progress over several decades has been evidenced in cancer therapy, there remains a need for the development of novel and effective therapeutic strategies to treat several relapsed and intractable cancers. In this regard, tubulin protein has become one of the efficient and major targets for anticancer drug discovery. Considering the antimitotic ability, several tubulin inhibitors have been developed to act against various cancers. Among various tubulin inhibitors available, combretastatin-A4 (CA-4), a naturally occurring lead molecule, offers exceptional cytotoxicity (including the drugresistant cell lines) and antivascular effects. Although CA-4 offers exceptional therapeutic efficacy, several new advancements have been proposed, in terms of structural modification via A and B rings, as well as cis-olefinic bridging, which provide highly efficient analogs with improved tubulin-binding efficiency to meet the anticancer drug development requirements. This review systematically emphasizes the recent trends and latest developments in the anticancer drug design and discovery using CA-4 analogs as the tubulin inhibiting agents by highlighting their structure-activity relationships (SAR) and resultant pharmacological efficacies.
尽管在癌症治疗方面已经取得了几十年的重大进展，但仍需要开发新的有效治疗策略来治疗几种复发和难治性癌症。在这方面，微管蛋白已成为抗癌药物发现的有效和主要靶标之一。考虑到抗有丝分裂能力，已经开发了几种微管蛋白抑制剂来对抗各种癌症。在现有的各种微管蛋白抑制剂中，天然存在的先导化合物 combretastatin-A4（CA-4）具有出色的细胞毒性（包括耐药细胞系）和抗血管生成作用。尽管 CA-4 具有出色的治疗效果，但已经提出了几项新的进展，包括通过 A 和 B 环进行结构修饰，以及顺式烯烃桥接，这些都提供了具有更高微管结合效率的高效类似物，以满足抗癌药物开发的要求。本综述通过强调其结构-活性关系（SAR）和由此产生的药理功效，系统地强调了使用 CA-4 类似物作为微管蛋白抑制剂的抗癌药物设计和发现的最新趋势和最新进展。
