Design, synthesis, modeling studies and biological screening of novel pyrazole derivatives as potential analgesic and anti-inflammatory agents.

Autor: Taher AT; Cairo University, Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Cairo, Egypt; October 6 University (O6U), Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, 6th of October City, Giza, Egypt., Mostafa Sarg MT; Al-Azhar University, Faculty of Pharmacy, Organic Chemistry Department (Girls), Cairo, Egypt., El-Sayed Ali NR; Misr University for Science and Technology, Faculty of Pharmacy, Organic Chemistry Department, Giza, Egypt., Hilmy Elnagdi N; Modern University for Technology and Information, Faculty of Pharmacy, Organic Chemistry Department, Cairo, Egypt. Electronic address: Elnagdinoha@yahoo.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Aug; Vol. 89, pp. 103023. Date of Electronic Publication: 2019 May 31.
DOI: 10.1016/j.bioorg.2019.103023
Abstrakt: Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of carbon chain in different pyrazole derivatives bearing various amine moieties. Combination of pyrazoline ring with either pyrazole or quinoline rings (Floctafenine derivatives) through synthesis of chalcones and their cyclization into pyrazolines was involved. The structures of target compounds were confirmed by elemental analysis and spectral data. All the newly synthesized compounds were investigated for their anti-inflammatory and analgesic activities compared to Indomethacin as a reference drug. Docking and molecular modeling study was initiated to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior of the most potent compounds 14b, 15b and 22 through their various interactions with the active site of COX-2 isozyme. Protein Data Bank (PDB) file of COX II enzyme with the code 4Z0L and its co-crystallized ligand Indomethacin were used for this purpose. The binding affinity was evaluated via comparing the scoring energy (S) and amino acid interactions of novel compounds with Indomethacin.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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