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Novel Anti‐Caner Nucleoside Analogs: Synthesis and Activity
Author(s) -
Abdullah Rola Hassan,
Hamzeh Khalil,
Bouhadir Kamal,
Eid Ali
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02415
Subject(s) - colorectal cancer , cell growth , chemistry , cell adhesion , adhesion , cancer research , pharmacology , cancer , cell , biochemistry , medicine , organic chemistry
Cancer continues to be the second leading cause of death worldwide, with colorectal cancer (CRC) being the second most common type. Despite significant advances in cancer therapies, current treatment of CRC remains inefficient. In addition, effectiveness of currently available chemotherapeutic drugs such as 5‐FlouroUracil (5FU) is limited owing to developed resistance in CRC. Here, we provide novel schemes for synthesis of four novel nucleoside analogs, as well as describe their effects on proliferation, migration, aggregation, adhesion and de‐adhesion of human colorectal cancer cells, both wild‐type and 5‐FU‐resistant HCT116. In either cell type, our synthesized novel analogs significantly inhibited cell viability in a concentration and time‐dependent manner. Importantly, all the four analogues inhibited proliferation at a much lower concentration than that of 5FU, indicating higher potency of these analogs. In addition, these compounds inhibited cell migration in a time‐dependent manner. They also inhibited adhesion and de‐adhesion of both cell types to collagen, as well as promoted homotypic cell‐cell interaction. ERK1/2 and iNOS were both inhibited by these analogs. This was also concomitant with a decrease in the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF), as well as a decrease in MMP‐2 and MMP‐9 release. Taken together, by inhibiting these hallmarks of malignancy, our data highlight that the four analogs could act as potent chemotherapeutic drugs against CRC, including the resistance form.