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.
Highlights
Inflammation is defined as the reaction to (a) invasion of an infectious agent, (b)a challenge by an antigen, or (c) even a simple physical injury [1,2]
Several other mediators are released among which neurotransmitters such as the substance P (SP) [4] of the tachykinin family and the calcitonin gene-related peptide (CGRP) which may be involved in vasodilation and increased vascular permeability
According to the According to the results, all compounds exhibited a probability, Pa, to show antiresults, all compounds exhibited a probability, Pa, to show anti-inflammatory action beinflammatory action between 0.274 and 0.636, a high enough probability to encourage tween 0.274 and 0.636, a high enough probability to encourage the experimental evaluation the experimental evaluation of the compounds
Summary
Inflammation is defined as the reaction to (a) invasion of an infectious agent, (b). a challenge by an antigen, or (c) even a simple physical injury [1,2]. Antibiotics [8,9,10], local anesthetics [11], anti-inflammatory [12,13,14,15], analgesic and antipyretics [16], anti-HIV [17,18], antiallergic [19], antihypertensives [20] against schizophrenia [21] and hypnotics [22] Some drugs, such as meloxicam, a new NSAID [23], the sulfathiazole, simple sulfonamide antibacterial, as well as niridazole, stronger medicine drug against schistosomiasis [24] contain thiazole ring in its molecules. The current version of PASS predicts more than 7900 types of biological activity including pharmacotherapeutic effects, mechanisms of action, interaction with drug-metabolizing enzymes, side effects, and toxicity [2,8]
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