Poster
58

Synthesis, cytotoxicity, and tubulin polymerization inhibitory activity of novel pyrrolone and pyridazinone derivatives

Discussion

In this project we are concerned with the design and discovery of selective anticancer agents, namely, vascular disrupting agents (VDAs) that work by acting near thecolchicine binding site of the β subunit of endothelial cell tubulin, resulting indepolymerization of microtubules and disorganization of actin and tubulin. Endothelialcells of the tumor vasculature undergo apoptosis resulting in blood flow shutdown andmassive tumor necrosis. We are working to synthesize novel vascular disrupting agentsof enhanced solubility in aqueous biological media, and longer shelf life thancombretastatin A4 (CA-4). In addition to, ease of synthesis from less expensivematerials to get medicines of affordable prices. The biological activity of the candidatecompounds will be evaluated by different techniques like, effects on culture humancancer cell growth, flow cytometry, Indirect Immunofluorescence, tubulinpolymerization inhibition by tubulin assembly assay techniques, and electronmicroscopy. Also, molecular docking experiments of the potent anticancer analogueswith the ligand binding site of colchicines or CA-4 using recent software modelingprograms will be performed.

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