Details

Autor(en) / Beteiligte

• Reddy, M. Amarnath
• Jain, Nishant
• Yada, Deepthi
• Kishore, Chandan
• Vangala, Janakiram Reddy
• P. Surendra, Reddy
• Addlagatta, Anthony
• Kalivendi, Shasi V
• Sreedhar, Bojja

Titel

Design and Synthesis of Resveratrol-Based Nitrovinylstilbenes as Antimitotic Agents

Ist Teil von

• Journal of medicinal chemistry, 2011-10, Vol.54 (19), p.6751-6760

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.