Synthesis, preliminary pharmacological evaluation, molecular docking, and ADME studies of new 4-thiazolidinone derivatives bearing ketoprofen moiety targeting cyclooxygenase enzyme

Allawi, Mustafa M.; Mahdi, Monther F.; Raoof, Ayad M. R.

doi:10.21608/ejchem.2021.71012.3561

Synthesis, preliminary pharmacological evaluation, molecular docking, and ADME studies of new 4-thiazolidinone derivatives bearing ketoprofen moiety targeting cyclooxygenase enzyme

Document Type : Original Article

Authors

¹ Department of Pharmacy, Uruk University College, Baghdad, Iraq

² pharmaceutical chemistry department, college of pharmacy, university of almustansyria, Baghdad, Iraq

³ Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mustansiriyah, Baghdad, Iraq.

10.21608/ejchem.2021.71012.3561

Abstract

Thiazolidinone, a saturated form of thiazole with a carbonyl group on fourth carbon, has been considered as a magic moiety (wonder nucleus) that possesses almost all types of biological activities. A new series of 4-thiazolidinones bearing ketoprofen moiety had been designed, then synthesized by reacting Schiff-base with chloroacetic acid and sodium acetate in ethanol according to Baldwin rules for ring closure and finally evaluated as a potent cyclooxygenase-2 (COX-2) inhibitors.
Characterization and identification of the synthesized compounds were established by the determination of 1H-NMR spectra,13C-NMR, FT-IR spectroscopy, and physical properties.
These newly synthesized compounds have been evaluated in vivo for their anti-inflammatory efficiency and In silico selectivity toward COX-2 through molecular docking by using GOLD suite v.5.6.2. All the tested compounds via molecular docking showed anti-inflammatory activity and some of them have significant activity when compared with diclofenac, and ketoprofen as referenced drugs because of having hydrogen bonding interaction toward the key amino acids within COX isozymes Tyr355, and Met522, and all these results were compatible with the study of in vivo acute anti-inflammatory activities for tested compounds.
Also, ADME studies had been accomplished to predict which compounds are a candidate to be taken orally, absorption sites, bioavailabilities, topological polar surface area(TPSA), and also drug-likeness. The ADME results reported that all the synthesized compounds can be absorbed from GIT.
The objective of this work is to synthesize and initial pharmacological assessment of new derivatives of ketoprofen by studying their interactions with COX-1 and COX-2 by docking and to determine some relationships between their structures and biological activity. Incorporating of the 4-thiazolidinone nucleus into ketoprofen moiety to increase the selectivity toward COX-2. Comparing the In silico results with In vivo results by using egg white to induce acute inflammation. The anti-inflammatory assessment was done for six final compounds.

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