Design, synthesis and biological evaluation of chromenopyrimidines as potential cytotoxic agents

Future Medicinal Chemistry
Nehal M El-BakhshawangyAzza T Taher

Abstract

The design and synthesis of chromenopyrimidines as microtubule destabilizing agents. Novel chromenopyrimidines and chromenotriazolopyrimidines were prepared and evaluated for their cytotoxicity against MCF-7 cell line. The most potent compound was tested for its possible effect on tubulin inhibition, cell cycle distribution, apoptosis initiation and caspase-3 activation. All the prepared compounds showed potent cytotoxic activity. Compound 13 was the most prominent (IC50 = 0.13 μM on tumor cell line MCF-7 and 14.06 μM on mammary epithelial cell line MCF-10A). Compound 13 inhibited tubulin polymerization (IC50 = 8.39 μM), caused cell cycle arrest at G2/M phase (fivefold more than control) and cellular apoptosis. Compound 13 increased the level of active caspase-3, 12-fold compared with control.

References

Oct 14, 2000·Annual Review of Cell and Developmental Biology·K H Downing
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
May 17, 2005·Current Pharmaceutical Design·Youngjae You
Oct 13, 2009·Mini Reviews in Medicinal Chemistry·Jing ChenYongzhou Hu
Oct 13, 2011·ChemMedChem·Alberto MassarottiAndrea Brancale
Nov 19, 2011·Bioorganic & Medicinal Chemistry·Christoph NitscheChristian D Klein
Jul 21, 2012·Pharmaceutical Research·Yan LuDuane D Miller
Jul 25, 2012·ACS Combinatorial Science·Anatoliy M ShestopalovVictor V Semenov
Dec 12, 2012·European Journal of Medicinal Chemistry·Manal M KandeelHeba A H Elshemy
Sep 21, 2013·Future Medicinal Chemistry·Shivaputra A PatilDuane D Miller
Jan 27, 2015·Current Medicinal Chemistry·Ya-Ting JiZhao-Peng Liu
Sep 24, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Souvik BanerjeeDuane D Miller
Oct 21, 2015·Analytical Cellular Pathology (Amsterdam)·Daniele FanaleViviana Bazan
Dec 27, 2015·Pharmacology & Therapeutics·Ying ZhaoGuanhua Du
Feb 24, 2016·Anti-cancer Agents in Medicinal Chemistry·Xiaoxin WuWei Li
Oct 12, 2016·Chemistry : a European Journal·Xiang YuHui Xu
Nov 10, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Souvik BanerjeeDuane D Miller

❮ Previous
Next ❯

Methods Mentioned

BETA
MDAs
NMR
ELISA
flow cytometry

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis