Next Generation Antineoplastic Agents: A Review on Structurally Modified Vinblastine (VBL) Analogues

Abstract

Background: Throughout the history of human civilizations, cancer has been a major health problem. Despite the advancements made by modern medical sciences, complete treatment or removal of cancerous cells is still a challenging task. Vinblastine, an alkaloid obtained from Catharanthus roseus (L.) G. Don is one of the prominent antineoplastic agents that is being clinically used. To improve the biological potential and reduce sideeffects of this structurally complex molecule, several related analogues have been reported. The present article reviews recently reported structurally modified vinblastine analogues and its impact on biological activity. Methods: We carried out a comprehensive database search on recently reported vinblastine analogues. Both upper (catharanthine) and lower (vindoline) structural units have been considered. The role of functional group modification on anticancer activities has been discussed. In addition, formulations based on vinblastine being considered by NIH, USA for different types of cancers have also been discussed. Results: Around fifty papers were included in the review, including computational and experimental ones. These papers were analysed to discuss the mechanism of action of the parent vinblastine molecule and their analogues. The importance of each functionalities on its anticancer activity have been discussed. This reviewed identified the potential sites of vinblastine core where modification led to improved anticancer activity. Furthermore, several new formulations have also been discussed which are under different phases of clinical trial. Conclusion: The present article highlights the importance of vinblastine in cancer chemotherapy. Literature survey confirms that it is now possible to synthesize new molecules with activity in picomolar range. Not only the periphery of the molecule, the core structure of this magical molecule can be modified to achieve next generation antineoplastic agents.