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AuthorHamze, Khalil
AuthorAbdallah, Rola H
AuthorYounis, Nour K
AuthorFardoun, Manal
AuthorDarwiche, Nadine
AuthorKobeissy, Firas
AuthorIratni, Rabah
AuthorBouhadir, Kamal
AuthorEid, Ali H
Available date2023-01-30T05:57:04Z
Publication Date2022-09-14
Publication NameCurrent Medicinal Chemistry
Identifierhttp://dx.doi.org/10.2174/0929867329666220914112042
CitationHamze Khalil, Abdallah H. Rola, Younis K Nour, Fardoun Manal, Darwiche Nadine, Kobeissy Firas, Iratni Rabah, Bouhadir Kamal*, Eid H. Ali*, 2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-sensitive and Resistant Colorectal Cancer Cells, Current Medicinal Chemistry 2023; 30() . https://dx.doi.org/10.2174/0929867329666220914112042
ISSN0929-8673
URIhttp://hdl.handle.net/10576/39167
AbstractCancer continues to be the second leading cause of death worldwide with colorectal cancer (CRC) being the third most common type. Despite significant advances in cancer therapies, current treatment of CRC remains suboptimal. In addition, the effectiveness of available chemotherapeutic drugs such as 5-Fluorouracil (5-FU) is limited by CRC-acquired resistance. In this study, we provide innovative approaches employed in synthesizing four novel nucleobase analogs. Equally, we describe the effects of these compounds on proliferation, migration, aggregation, adhesion of 5-FU-sensitive (HCT116) and -resistant (5-FU-R-HCT116) human CRC cells. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration- and time-dependent manner. This highlights the higher potency of these novel analogs. In addition, these compounds attenuated migration and adhesion of both cell types, while they promoted homotypic cell-cell interaction. These changes were reflected by the downregulation matrix metalloproteases (MMP-2 and MMP-9). Furthermore, our analogs exhibited a potent anti-angiogenic activity in vivo. In addition, these compounds reduced the level of secreted vascular endothelial growth factor (VEGF) and nitric oxide (NO) production in both 5-FU-sensitive and -resistant cells. Taken together, our data highlight the potential chemotherapeutic properties of our novel analogs against CRC, including the 5-FU-resistant form.
Languageen
PublisherBentham Science Publishers
Subject2-Nucleobase-substituted 4
5-Fluorouracil
6-Diamino-s-triazine analogues
Colorectal cancer
analogs
malignancy
nucleobase
Title2-Nucleobase-substituted 4,6-Diaminotriazine Analogs: Synthesis and Anti-cancer Activity in 5-Fluorouracil-Sensitive and Resistant Colorectal Cancer Cells.
TypeArticle
Pagination1-18
Volume Number30
ESSN1875-533X
dc.accessType Abstract Only


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