0

Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation

مارس 02, 2013

DOI:

Publisher: Dovepress

Bassem Sadek1 Amar Mansuor Hamruoni2 Abdu Adem1

Abstract: In this study, target compounds 5–12 were synthesized via acid amine coupling of ibuprofen and naproxen with methyl ester derivatives of amino acids, namely, l-proline, sarcosine, l-tyrosine, and l-glutamic acid. When tested for anti-inflammatory activity using the acute carrageenan-induced hind paw method in rats, compounds 5–12 showed significantly greater anti-inflammatory activity, in the range of 40.64%–87.82%, compared with a placebo control group (P , 0.001). Among the newly synthesized compounds 5–12, naproxen derivatives 9–12 with anti-inflammatory activity ranging between 66.99% and 87.82% showed significantly higher (P , 0.05) potency than ibuprofen derivatives 5–8 with inhibition in the range of 22.03%–52.91% and control groups of ibuprofen (76.34%) or naproxen (75.59%, P , 0.05). Moreover, derivatives 9–12 derived from naproxen, in particular compounds 9 and 10 which achieved 83.91% and 87.82% inhibition of inflammation, respectively, showed significantly (P , 0.05) higher potency than naproxen derivatives 11 and 12. Notably, among naproxen derivatives 9–12, the gastric ulcerogenicity for 9 (ulcer index 11.73) and 10 (ulcer index 12.30) was found to be significantly lower (P , 0.05) than that of the active ibuprofen and naproxen control groups with ulcer indices of 22.87 and 24.13, respectively. On the other hand, naproxen derivatives 9–11 showed significant inhibition (P , 0.05) of prostaglandin E2 synthesis when compared with the active control group receiving indomethacin, suggesting a correlation between the observed low ulcerogenicity and effect on prostaglandin E2 synthesis for compounds 9 and 10. However, significant inhibition of prostaglandin E2 observed for naproxen derivative 11 (107.51) did not correlate with its observed ulcer index (16.84). Our overall findings for carbamoylmethyl ester derivatives named 5–12 clearly suggest that the compounds showing potent antiinflammatory effect. Keywords: carbamoylmethyl ester, anti-inflammatory, prostaglandin E2, inhibitory propertie

Other Researches

Osteoporosis Related Knowledge and Attitudes: The Scenario in Tripoli, Libya

Abstract: Background: Osteoporosis is a worldwide disease, which is characterized by a reduction in bone mass and alteration of its architecture that increases bone fragility and the risk of fracture. Objective: This study aimed to assess knowled...

Molecualr modelling studies on alpha-7 nicotinic receptor allosteric modulators yields novel filter-based virtual screening protocol

The ɑ7 receptor is a member in the nicotinic acetylcholine receptor (nAChR) which has been implicated in several neurological disorders. Beside normal agonists and antagonists of α7 nAChRs, several studies revealed other types of molecules that are ...

The hypoglycemic effect of Libyan Truffle (Terfezia Boudieri) in experimentally induced diabetic rats.

.Recent studies have shown that many types of mushrooms may have important physiological functions in humans including antioxidant activities, regulation of blood lipid level and blood glucose level. The present study was designed to investigate the...

Risk calculation of developing type 2 diabetes in Libyan adults

The aim of this study was to identify nationals at risk of developing type 2 diabetes within the next 10 years in some areas across Tripoli Health Authority in Libya. In this questionnaire-based survey, a total of 400 Libyan nationals of both gender...

Synthesis of 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones: Selective antagonists of muscarinic (M3) receptors

Two approaches to tetrahydro-[1H]-2-benzazepin-4-ones of interest as potentially selective, muscarinic (M(3)) receptor antagonists have been developed. Base promoted addition of 2-(tert-butoxycarbonylamino)methyl-1,3-dithiane with 2-(tert-butyldimet...

Investigation of the mechanism for the relaxation of rat duodenum mediated via M1 muscarinic receptors

1 Relaxation responses of the rat isolated duodenum to the putative M1 muscarinic receptor agonist, McN-A-343, were examined to determine whether the response was due to the release of known non-adrenergic, non-cholinergic relaxant neurotransmitters...