Amino acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, In Silico and In Vitro Studies

Cetin A., Donmez A., Dalar A., Bildirici İ.

ChemistrySelect, cilt.8, sa.6, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 6
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/slct.202204926
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: ADMET, Antioxidants, Drug discovery, Enzymes, Pharmacokinetics
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

© 2023 Wiley-VCH GmbH.Pancreatic lipase (PL) inhibitors have received considerable attention by several researchers because of its ability to hydrolyse the triglycerides in the small intestine. This study reports the (i) synthesize of new pyrazole derivatives binding amino acid and Dicyclohexylurea (DCU), (ii) their pharmaceutical potentials- via enzyme inhibitory activity towards PL and antioxidant activities (using complementary antioxidant methods including FCR, FRAP and ORAC), (iii) the possible interactions between pyrazole compounds and PL enzyme through in silico studies, and the pharmacokinetic properties of the tetra-substituted pyrazole analogues by PreADMET. Enzyme activities with IC50 values of the pyrazole analogues were found to be in a high range of 6.6±0.4 μM to 13.5±0.2 μM. However, antioxidant activities of the pyrazole analogues exhibited low binding affinities against FCR, FRAP, and ORAC. The pyrazole analogues with docking scores were in the range of −7.3 to −15.2 and their SAR analysis were demonstrated to highlight the importance of amino acid and DCU linked scaffolds. Two web tools were utilized for the purpose of predicting ADMET parameters of drugs and drug-like pyrazole analogues. These results suggested that the amino acid and DCU linked pyrazole analogues have potential as PL inhibitors.