Preparation, DFT calculations, docking studies, antioxidant, and anticancer properties of new pyrazole and pyridine derivatives

Zebbiche Z., Sekerci G., Boulebd H., KÜÇÜKBAY F., TEKİN S., Tekin Z., ...Daha Fazla

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.36, sa.9, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 9
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1002/jbt.23135
  • Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: anticancer activity, antioxidant activity, DFT and docking studies, pyrazole derivatives, pyridine derivatives, DENSITY-FUNCTIONAL THEORY, RAPID COLORIMETRIC ASSAY, BIOLOGICAL EVALUATION, ANTIBACTERIAL, INHIBITORS, DISCOVERY, HYBRIDS, DESIGN, BENZIMIDAZOLE, SURVIVAL
  • İnönü Üniversitesi Adresli: Evet

Özet

Seven novel pyrazole derivatives (4a-g) and four novel starting compounds incorporating substituted pyridine moieties were synthesized successfully. Cell viability assay for the tested compounds was performed, and the inhibitory concentrationlogarithmic 50 (LogIC(50)) values of the compounds were calculated after a 24-h treatment. Four of the examined compounds (3d, 3g, 4f, and 4g) showed comparable cytotoxic activity against CaCo-2 compared to the standard drug docetaxel at 0.1 and 1 mu M concentrations. Although the LogIC(50) of docetaxel was -0.678 mu M for CaCo-2 cells at 24 h, the LogIC(50) values of compounds were -0.794, -0.567, -0.657, and -0.498 respectively. Five of the compounds (2d, 2g, 3d, 3g and 4e) showed comparable cytotoxic activity against MCF-7 at 0.1 mu M concentration compared to docetaxel (p < 0.05). Docking studies revealed the compounds have a good affinity to the active site of the human topoisomerase II beta enzyme. The antioxidant capacities of all compounds were determined using both 1,1-diphenyl-2-picrylhydrazyl and metal chelation methods. Although the compounds did not show significant antioxidant activity, relatively effective are compounds 3c, 3d, and 3g, which are hydrazine derivatives with approximately 50% antioxidant activity of standard antioxidants at concentrations of 62.5 and 125 mu g/ml.