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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cancer Biology

Background:

• Combretastatin A-4 (CA-4) is a potent natural product with significant cytotoxic activity, serving as a lead compound for microtubule targeting agents.
• Microtubule targeting agents are vital in cancer chemotherapy, but resistance and toxicity remain challenges.
• Recent research (2016-2023) explores novel CA-4 analogues to improve anticancer efficacy and overcome limitations.

Purpose of the Study:

• To provide a comprehensive chronological overview of CA-4 analogue development from 2016 to early 2023.
• To discuss design strategies, structure-activity relationships, synthesis, and binding interactions of promising CA-4 analogues.
• To highlight the anticancer potential and clinical application limitations of these analogues, suggesting strategies for improvement.

Main Methods:

• Literature review focusing on CA-4 analogues developed between 2016 and early 2023.
• Analysis of design strategies, structure-activity relationships, and synthesis pathways.
• Evaluation of cytotoxic activity, binding interactions, and biological anticancer activity.

Main Results:

• Numerous CA-4 analogues with diverse structural modifications have been synthesized and evaluated.
• Dual-targeting tubulin inhibitors demonstrate potential to overcome drug resistance and enhance synergistic efficacy.
• Linking CA-4 analogues with moieties like platinum (IV), amino acids, HDAC inhibitors, azetidin-2-one, pyrazole, sulfide, or selenium atoms yielded potent compounds.

Conclusions:

• CA-4 analogues represent a promising class of anticancer agents with diverse mechanisms of action.
• Innovative strategies, including dual targeting and conjugation with other therapeutic moieties, are crucial for enhancing efficacy and overcoming resistance.
• Further research into CA-4 analogues holds significant potential for advancing cancer chemotherapy.