Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity

• Thorough simplification of complex vinca alkaloid based on pharmacophore similarity has been conducted.
• A concise scheme for the syntheses of target compounds has been developed.
• Almost all the entities remain as antimitotic agent in the same manner as vinblastine.
• Structure–activity relationship was deeply discussed.

Thorough simplification of vinca alkaloids based on pharmacophore similarity has been conducted. A concise process for the syntheses of target compounds was successfully developed with yields from poor to excellent (19–98%). Cell growth inhibitory activities of these synthesized compounds were evaluated in five cancer cell lines including MCF-7, MDA-MB-231, HepG2, HepG2/ADM and K562. Almost all compounds exhibited moderate antitumor activity with optimal IC50 value of 0.89 ± 0.07 μM in MCF-7 cells. Investigation of structure–activity relationship (SAR) indicates that electron-withdraw substituents on the ring contribute to the enhancement of the antitumor activities. The simplified vinca alkaloids are confirmed as antimitotic agents, which inhibit the polymerization of tubulin just like vinblastine.

Thorough simplification of vinca alkaloid based on pharmacophore similarity has been conducted. The designed entity remains as antimitotic agent in the same manner of parent compound.Figure optionsDownload as PowerPoint slide