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Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold
Autorzy
Paulina Kasperkiewicz-Wasilewska
Rok wydania
2022
Czasopismo
International Journal of Molecular Sciences
Numer woluminu
23
Strony
11173/1-11173/24
DOI
10.3390/ijms231911173
Kolekcja
Język
Angielski
Typ publikacji
Artykuł
Cancer is one of the greatest challenges in modern medicine today. Difficult and long‐ term treatment, the many side effects of the drugs used and the growing resistance to treatment of neoplastic cells necessitate new approaches to therapy. A very promising targeted therapy is based on direct impact only on cancer cells. As a continuation of our research on new biologically active molecules, we report herein the design, synthesis and anticancer evaluation of a new series of N‐ Mannich‐base‐type hybrid compounds containing morfoline or different substituted piperazines moieties, a 1,3,4‐oxadiazole ring and a 4,6‐dimethylpyridine core. All compounds were tested for their potential cytotoxicity against five human cancer cell lines, A375, C32, SNB‐19, MCF‐7/WT and MCF‐7/DX. Two of the active N‐Mannich bases (compounds 5 and 6) were further evaluated for growth inhibition effects in melanoma (A375 and C32), and normal (HaCaT) cell lines using clono‐ genic assay and a population doubling time test. The apoptosis was determined with the neutral version of comet assay. The confocal microscopy method enabled the visualization of F‐actin reor‐ ganization. The obtained results demonstrated that compounds 5 and 6 have cytotoxic and proapoptotic effects on melanoma cells and are capable of inducing F‐actin depolarization in a dose‐ dependent manner. Moreover, computational chemistry approaches, molecular docking and elec‐ trostatic potential were employed to study non‐covalent interactions of the investigated compounds with four receptors. It was found that all the examined molecules exhibit a similar binding affinity with respect to the chosen reference drugs.
Słowa kluczowe
dimethylpyridine, N‐Mannich base, anticancer activity, cytotoxicity, molecular docking, non‐covalent interactions, 1,3,4-oxadiazole
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Pełny tekst licencji: https://creativecommons.org/licenses/by/3.0/pl/legalcode
Adres publiczny
http://dx.doi.org/10.3390/ijms231911173
Strona internetowa wydawcy
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