Browsing by Author "Donmez, Ali"

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Amino Acid and Dicyclohexylurea Linked Pyrazole Analogues: Synthesis, in Silico and in Vitro Studies
(Wiley-v C H verlag Gmbh, 2023) Cetin, Adnan; Donmez, Ali; Dalar, Abdullah; Bildirici, Ishak
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 mu M to 13.5 +/- 0.2 mu M. 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.
Tetra-Substituted Pyrazole Analogues: Synthesis, Molecular Docking, Admet Prediction, Antioxidant and Pancreatic Lipase Inhibitory Activities
(Springer Birkhauser, 2023) Cetin, Adnan; Donmez, Ali; Dalar, Abdullah; Bildirici, Ishak
The development of novel analogues for the pancreatic lipase (PL) inhibitors and antioxidant candidates remains a significant research objective, as these studies are essential to our understanding of the role of PL receptor in obesity. Herein, we report on the synthesis, molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, and biological evaluation of ten tetra-substituted pyrazole analogues as agents of PL inhibitors and antioxidant activities. The tetra-substituted pyrazole analogues displayed good binding affinity against Folin-Ciocalteu Reducing (FCR), Ferric Reducing Antioxidant Power (FRAP). However, the synthesized analogues displayed low binding affinity against Oxygen Radical Absorbance Capacity (ORAC). The tetra-substituted pyrazole analogues exhibited effective PL inhibition in the range of 2.0 +/- 0.0 and 34.3 +/- 0.3 mu M according to the enzyme assays. Furthermore, the detailed interactions and binding energies of the PL-tetra-substituted pyrazole analogues' complexes were determined using molecular docking studies. The binding energies of the PL-tetra-substituted pyrazole analogues' complexes were found in range of -9.4 to -13.2 kcal/mol. In addition, the ADMET predictions of tetra-substituted pyrazole analogues were carried out using PreADMET software. Overall, the obtained results revealed that antioxidant and PL inhibitory activities of tetra-substituted pyrazole analogues were in consensus with the ADMET predictions results.