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New 1,2,4-Triazole Derivatives with a N-Mannich Base Structure Based on a 4,6-Dimethylpyridine Scaffold as Anticancer Agents: Design, Synthesis, Biological Evaluation, and Molecular Modeling
Autorzy
Rok wydania
2025
Czasopismo
International Journal of Molecular Sciences
Numer woluminu
26
Strony
6572/1-6572/30
DOI
10.3390/ijms26146572
Kolekcja
Język
Angielski
Typ publikacji
Artykuł
A series of novel N-Mannich bases derived from a dimethylpyridine–1,2,4-triazole hybrid was synthesized and evaluated in vitro for cytotoxic activity on several human gastrointestinal cancer cells (EPG, Caco-2, LoVo, LoVo/Dx, and HT-29). Compound 6 bearing a phenyl group at the N-4 position and a 4-methylphenyl piperazine moiety at the N-2 position of the 1,2,4-triazole-3-thione scaffold exerted good cytotoxic activities on EPG and Caco-2 cell lines, along with pronounced selectivity, showing lower cytotoxicity against normal colonic epithelial cells (CCD 841 CoTr). Further evaluation revealed the good ability of compound 6 to inhibit the efflux function of P-glycoprotein in P-gp-expressing cell lines (HT-29, LoVo, and LoVo/Dx). Moreover, compound 6 induced apoptotic cell death through a significant increase in the caspase-3 and p53 protein levels in HT-29 cells. Finally, the molecular docking method was applied to explain our experimental findings. The molecular modeling study based on Density Functional Theory (DFT) and the Quantum Theory of Atoms in Molecules (QTAIM) analysis provided insight into the geometric and electronic structure properties of the compounds.
Słowa kluczowe
dimethylpyridine, atom, molecule, 4-triazole, N-Mannich base, anticancer activity, cytotoxicity, DFT, QTAIM, molecular docking
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Pełny tekst licencji: https://creativecommons.org/licenses/by/3.0/pl/legalcode
Adres publiczny
http://dx.doi.org/10.3390/ijms26146572
Strona internetowa wydawcy
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