2. Academic Validation
  3. Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity

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

  • Eur J Med Chem. 2013 Jul:65:158-67. doi: 10.1016/j.ejmech.2013.04.057.
Jing Zheng 1,  Lijuan Deng,  Minfeng Chen,  Xuzhi Xiao,  Shengwei Xiao,  Cuiping Guo,  Gaokeng Xiao,  Liangliang Bai,  Wencai Ye,  Dongmei Zhang,  Heru Chen
Affiliations

Affiliation

  • 1 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
PMID: 23708010 DOI: 10.1016/j.ejmech.2013.04.057
Abstract

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.

Keywords

Anticancer; Antimitotic agent; Pharmacophore similarity; Vinca alkaloid.

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