Discovery of Novel Small-Molecule Compounds with Selective Cytotoxicity for Burkitt’s Lymphoma Cells Using 3D Ligand-Based Virtual Screening

Molecules

Martina Gobec²  Izidor Sosič²  Boris Brus²  Aleš Obreza²  Stanislav Gobec¹ 

[1] University of Ljubljana, Faculty of Pharmacy, Aškerčeva cesta 7, Ljubljana 1000, Slovenia;

关键词: Burkitt’s lymphoma;    ligand-based;    similarity search;    selectivity;   

DOI  :  10.3390/molecules191119209

来源: mdpi

【 摘 要 】

We describe a ligand-based approach towards compounds with more specific targeting for Burkitt’s lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that one compound has better growth inhibition and improved selectivity towards Burkitt’s lymphoma cells than the query compound. However, initial mechanism-of-action studies show a different target profile in comparison with the previous hit compound, which does not involve the inhibition of the proteasome or the NFκB pathway. The data from this study provide a solid basis for further efforts in the search for selective agents against Burkitt’s lymphoma.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.