Drug Designing: Open Access
Open Access
ISSN: 2169-0138
ISSN: 2169-0138
Nazanin Namazi Sarvestani and Houri Sepehri
University of Tehran, Iran
Posters & Accepted Abstracts: Drug Des
The X-linked inhibitor of apoptosis protein inhibits the apoptotic executioner caspaseâ?3. In this study, a class of natural product was examined to elucidate its role in overcoming X-IAP-mediated inhibition of caspase-3. Eupatorin and salvigenin, two previously identified flavonoids demonstrated annexin-V binding to phosphatidylserine leading to cell cycle arrest in different phase and PARP cleavage in human colon cancer cell line. Second domain of XIAP (BIR2) contributes substantially to inhibition of caspases-3. A surface groove on BIR2 which also binds to Smac/DIABLO was targeted to inhibit XIAP. Mechanistic studies performed by molecular dynamic simulations (MDs) determined that the natural compounds are responsible for disintegration of hydrogen binding between Asp148 in BIR2 domain and caspase-3. Moreover, Eupatorin and salvigenin showed to removed critical salt bridge net between Asp148 residue and Arg233 and Phe228 at C terminal of BIR2 domain which is crucial for an appropriate anchoring by caspase-3.
Nazanin Namazi Sarvestani is currently a PhD student at University of Tehran, Iran. Her former research and scientific articles were based on Neuroscience and her recent thesis is on cancer. She has published 3 papers in reputed journals and wrote a book about medical physiology.
Email: nazanin.namazi@gmail.com