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. 2021 Jan 27;26(3):659.
doi: 10.3390/molecules26030659.

New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5 H)ones as Possible Anti-Inflammatory Agents

Christophe Tratrat  1 , Michelyne Haroun  1 , Aliki Paparisva  2 , Charalmpos Kamoutsis  3 , Anthi Petrou  2 , Antonis Gavalas  2 , Phaedra Eleftheriou  4 , Athina Geronikaki  2 , Katharigatta N Venugopala  1   5 , Hafedh Kochkar  6   7 , Anroop B Nair  1
Affiliations

New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5 H)ones as Possible Anti-Inflammatory Agents

Christophe Tratrat et al. Molecules. .

Abstract

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects.

Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock.

Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis.

Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

Keywords: COX; LOX; NDGA; anti-inflammatory; carrageenan; docking; thiazole; triazole.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Binding of flubriprofen at active center of COX-1 (A) and diclofenac at active center of COX-2 (B). Binding of naproxen to COX-2 active center (C).
Figure 2
Figure 2
(A) Binding of compound 3 into the active site of COX–1, (B) Binding of compound 8 into the active site of COX–1.
Figure 3
Figure 3
(A) Binding of 2 into the active site of COX–2, (B) Binding of 6 into the active site of COX–2.
See this image and copyright information in PMC

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