Design and synthesis of resveratrol-based nitrovinylstilbenes as antimitotic agents

Journal of Medicinal Chemistry
M Amarnath ReddyB Sreedhar

Abstract

A new series of resveratrol analogues was designed, synthesized, and demonstrated to be tubulin polymerization inhibitors. Most of these compounds exhibited antiproliferative activity and inhibited in vitro tubulin polymerization effectively at concentrations of 4.4-68.1 and 17-62 μM, respectively. Flow cytometry studies showed that compounds 7c, 7e, and 7g arrested cells in the G2/M phase of the cell cycle. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 7c and 7e. Docking of compounds 7c and 7e with tubulin suggested that the A-ring of the compounds occupies the colchicine binding site of tubulin, which coordinates with Cys241, Leu242, Ala250, Val318, Val328, and I378, and that the nitrovinyl side chain forms two hydrogen bonds with the main loop of the β-chain at Asn249 and Ala250.

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Citations

Aug 8, 2013·European Journal of Medicinal Chemistry·Zhiliang LvKe Li
Jan 15, 2013·European Journal of Medicinal Chemistry·A Suresh KumarB Sreedhar
Mar 8, 2017·ChemMedChem·Barbara De FilippisRosa Amoroso
Aug 19, 2014·Bioorganic & Medicinal Chemistry·Ahmed KamalNagula Shankaraiah
Apr 24, 2019·Journal of Asian Natural Products Research·Uppuluri Venkata MallavadhaniNishanth Jain
Jun 26, 2014·Organic & Biomolecular Chemistry·Guobing YanLianggui Wang
Oct 28, 2014·Chemical Communications : Chem Comm·Can XueShengming Ma
Apr 22, 2017·Molecular Diversity·Zulfiqar Ali KhanSohail Anjum Shahzad

Related Concepts

resveratrol-3-sulfate
Cell Nucleus
Dye Exclusion Assays, Antitumor
Enzyme Activation
Microtubules
Nitrated Compounds
Molecular Stereochemistry
Stilbenes
Structure-Activity Relationship
Vinyl Compounds

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