Combretastatin A-4 based compounds as potential anticancer agents: A review.

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI:10.1016/j.bioorg.2024.107930

Mai H Omar, Soha H Emam, Demiana S Mikhail, Salwa Elmeligie

引用次数: 0

Abstract

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.

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以联合他汀 A-4 为基础的化合物作为潜在的抗癌剂：综述。

本综述讨论了作为微管靶向药物先导化合物的考布他丁 A-4（CA-4）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的地位。本综述讨论了有前景的 CA-4 类似物的设计策略、结构-活性关系、合成、细胞毒性活性和结合相互作用等全貌，并按时间顺序排列了从 2016 年到 2023 年初的时间。此外，本综述还强调了它们作为抗癌药物的生物活性，并概述了临床应用的局限性和建议的克服策略。双靶向微管蛋白抑制剂显示出超越耐药性和提供协同疗效的巨大潜力。将铂 (IV)、氨基酸和 HDAC 靶向分子与活性微管蛋白抑制剂连接，可产生强效的活性化合物。与氮杂环丁烷-2-酮、吡唑、硫化物或携带硒原子桥接的 CA-4 类似物通过不同途径对多种恶性细胞系产生细胞毒性作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.