Open Access15-LOX Inhibitors: Biochemical Evaluation of Flurbiprofen and its Derivatives
Author(s) -
Saghir Abbas,
Sumera Zaib,
Saqib Ali,
Jamshed Iqbal
Publication year - 2020
Publication title -
life and science
Language(s) - English
Resource type - Journals
eISSN - 2708-2970
pISSN - 2521-0475
DOI - 10.37185/lns.1.1.107
Subject(s) - flurbiprofen , docking (animal) , chemistry , protein data bank (rcsb pdb) , active site , stereochemistry , molecule , propanoic acid , combinatorial chemistry , pharmacology , enzyme , biochemistry , organic chemistry , medicine , nursing
Objective: The synthesis, characterization, 15-LOX inhibition and molecular docking studies of a commercially available NSAID, flurbiprofen and its derivatives. Study Design: Experimental study. Place and Duration of Study: The study was carried out at Quaid-i-Azam University and Centre for Advanced Drug Research COMSATS University Islamabad, Abottabad Campus from March 2019 to February 2020. Materials and Methods: The structural elucidation of the compounds (2-5) was carried out using infrared, 1H and 13C NMR spectroscopic studies. The structure of 4-amino-5-(1-(2-fluorobiphenyl-4-yl)-ethyl)-4H-1,2,4- triazole-3-thione (5) was also verified by single crystal X-ray diffraction (XRD) studies. Results: The most potent inhibitor for 15-LOX (2) has an IC50value of0.18 ± 0.01 μM. Molecular docking results of 1, 2, 3 and cognate ligand inside the active site of 15-LOX (PDB ID: 1IK3) revealed significant correlation. Conclusion: This work represents cost-effective, reproducible and facile conversion of an aromatic monocarboxylic acid into potent derivatives.The molecules 2-(2-fluorobiphenyl-4-yl) propanoic acid (1) and its derivatives (2-5) possess 15-LOX inhibition and can be a prospective therapeutic target for chronic obstructive pulmonary disease.