COX Inhibition Profile and Molecular Docking Studies of Some 2-(Trimethoxyphenyl)-Thiazoles
| Autor: | Alexandra M. Crăciun, Liliana Pacureanu, Elena-Luminita Crisan, Cristina Ioana Stoica, Laurentiu Răzvan Rusu, Smaranda Oniga, Cătălin Araniciu, Mariana Palage |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
selective COX-2 inhibition NSAIDs Amino Acid Motifs Thiazines Pharmaceutical Science 2-(trimethoxyphenyl)-thiazoles molecular docking Pharmacology Meloxicam 01 natural sciences Analytical Chemistry law.invention law Drug Discovery biology Chemistry Anti-Inflammatory Agents Non-Steroidal Molecular Docking Simulation Chemistry (miscellaneous) Recombinant DNA Molecular Medicine Thermodynamics Hydrophobic and Hydrophilic Interactions medicine.drug Protein Binding Gene isoform Article lcsh:QD241-441 03 medical and health sciences Structure-Activity Relationship Pharmacokinetics Phenols lcsh:Organic chemistry In vivo medicine Animals Humans Cyclooxygenase Inhibitors Protein Interaction Domains and Motifs Physical and Theoretical Chemistry Binding site Binding Sites Sheep 010405 organic chemistry Organic Chemistry Hydrogen Bonding In vitro 0104 chemical sciences Kinetics Thiazoles 030104 developmental biology Cyclooxygenase 2 biology.protein Cyclooxygenase 1 Cyclooxygenase |
| Zdroj: | Molecules, Vol 22, Iss 9, p 1507 (2017) Molecules; Volume 22; Issue 9; Pages: 1507 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry |
| ISSN: | 1420-3049 |
| Popis: | Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID. |
| Databáze: | OpenAIRE |
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