Discovery of novel small-molecule compounds with selective cytotoxicity for Burkittʼs lymphoma cells using 3D ligand-based virtual screening

Gobec, Martina (author), Sosič, Izidor (author), Brus, Boris (author), Obreza, Aleš (author), Gobec, Stanislav (author), Mlinarič-Raščan, Irena (author)

We describe a ligand-based approach towards compounds with more specific targeting for Burkittʼs 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 Burkittʼs 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 Burkittʼs lymphoma.

• Language: English
• Keywords: Burkittʼs lymphoma, ligand-based, similarity search, selectivity
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2014
• Number of pages: Str. 19209-19219
• Numbering: Vol. 19, iss. 11
• PID: 20.500.12556/RUL-130508
• UDC: 616-006.44
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules191119209
• COBISS.SI-ID: 3776113
• Publication date in RUL: 15.09.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 19.11.2014

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin