A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

Bioorg Chem. 2018 Dec 05;84:399-409

Authors: Mohamed KO, Zaki I, El-Deen IM, Abdelhameid MK

Abstract
A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [3H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7.

PMID: 30551066 [PubMed - as supplied by publisher]

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