Exploring the anticancer potential of new 3-cyanopyridine derivatives bearing N-acylhydrazone motif: Synthesis, DFT calculations, cytotoxic evaluation, molecular modeling, and antioxidant properties
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
3-Cyanopyridine derivatives are known for exhibiting excellent anticancer activity due to their strong capability to inhibit various biological targets, including Pim-1 kinase, survivin, and tubulin polymerization. On the other hand, N-acylhydrazones (NAH) are known to be a very versatile motif in medicinal chemistry and drug design. Based on these data, we report in this paper, the synthesis of novel 3-cyanopyridines incorporating N-acyl hydrazine scaffold, the evaluation of their cytotoxicity on the breast (MCF-7) and ovarian (A-2780) cancer cell lines and their antioxidant properties. Excluding 4a and 4d, all tested molecules exhibited high cytotoxicity against A-2780, with IC50 values ranging from 1.14 to 1.76 mu M. Conversely, only four molecules 3d, 4b, 4c, and 4d demonstrated cytotoxicity against MCF-7, with IC50 values ranging from 1.14 to 3.38 mu M. On the other hand, all the tested molecules exhibited a moderate antioxidant capacity in both the DPPH and metal chelation assays. Docking and molecular dynamics studies revealed that 2d, 3d, and 4d are potential inhibitors of tubulin and the oe strogen receptor, which may explain their high cytotoxicity. These results are promising to study these newly synthesized 3-cyanopyridine-N-acylhydrazones in depth for use as potential anticancer candidates. A series of novel N-acetylhydrazone motifs-containing 3-cyanopyridine derivatives were synthesized, and their anticancer properties against MCF-7 and A2780 cancer cell lines, along with their antioxidant capacities, were investigated under in vitro conditions. Additionally, density functional theory (DFT) calculations and molecular modeling were conducted in silico. image
Açıklama
Anahtar Kelimeler
3-cyanopyridine, antioxidant, cytotoxicity, docking, MCF-7 and A-2780, molecular dynamics, N-acylhydrazone
Kaynak
Journal of Biochemical and Molecular Toxicology
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
38
Sayı
9
