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- Title
Pyridine-Ureas as Potential Anticancer Agents: Synthesis and In Vitro Biological Evaluation.
- Authors
El-Naggar, Mohamed; Almahli, Hadia; Ibrahim, Hany S.; Eldehna, Wagdy M.; Abdel-Aziz, Hatem A.; Collina, Simona; Miloso, Mariarosaria
- Abstract
In our endeavor towards the development of effective anticancer agents, a novel series of pyridine-ureas <bold>8a</bold>–<bold>n</bold> were synthesized. All the newly prepared derivatives were evaluated in vitro for their growth inhibitory activity towards the proliferation of breast cancer MCF-7 cell line. Compounds <bold>8e</bold> and <bold>8n</bold> were found to be the most active congeners against MCF-7 cells (IC50 = 0.22 and 1.88 µM after 48 h treatment; 0.11 and 0.80 µM after 72 h treatment, respectively) with increased activity compared to the reference drug doxorubicin (IC50 = 1.93 µM). Moreover, eight selected pyridines <bold>8b</bold>, <bold>8d</bold>, <bold>8e</bold>, <bold>8i</bold>, <bold>8j</bold> and <bold>8l</bold>–<bold>n</bold> were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Pyridines <bold>8b</bold> and <bold>8e</bold> proved to be the most effective anticancer agents in the NCI assay with mean inhibition = 43 and 49%, respectively. Both <bold>8b</bold> and <bold>8e</bold> exhibited anti-proliferative activity against all tested cancer cell lines from all subpanels growth inhibition (GI for <bold>8b</bold>; 12–78%, GI for <bold>8e</bold>; 15–91%). Pyridines <bold>8b</bold> and <bold>8e</bold> were screened in vitro for their inhibitory activity against VEGFR-2. Both compounds inhibited VEGFR-2 at micromolar IC50 values 5.0 ± 1.91 and 3.93 ± 0.73 µM, respectively. The most active pyridines were filtered according to the Lipinski and Veber rules and all of them passed these filters. Finally, several ADME descriptors were predicted for the active pyridines through a theoretical kinetic study.
- Subjects
PYRIDINE; ANTINEOPLASTIC agents; CELL proliferation; INSULIN derivatives; DOXORUBICIN
- Publication
Molecules, 2018, Vol 23, Issue 6, p1459
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23061459