title: Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and prostaglandin E2 inhibitory properties.
abstract: A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl) benzamides (1a-h) were synthesized via reaction of 2-((4-ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several substituted primary aromatic amines. The new compounds were characterized by proton nuclear magnetic resonance ((1)H-NMR), carbon-13 nuclear magnetic resonance ((13)C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and elemental analysis. The anti-inflammatory activity of 1a-h was investigated by acute carrageenan-induced paw edema in mice using the reference drug indomethacin. The results obtained indicated that, of the derivatives developed, 1a and 1d-h exhibited significantly higher anti-inflammatory activity (26.81%-61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490 for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the indomethacin group (in which the ulcer incidence was 80%). Of particular note, the ulcer index of 0.2 for 1e was significantly less than that in the indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2) inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly different from those of the placebo group (530.13 pg/mL, P < 0.001), and equipotent to the effect observed in the indomethacin-pretreated group (96.13 pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also significantly different from that of the placebo group (P < 0.001) and of the indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with 1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences. Our overall findings for N-phenylcarbamothioylbenzamides 1a-h clearly suggest that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2 synthesis, and markedly demonstrate low ulcer incidence.
authors.affiliation: Department of Pharmaceutical Chemistry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Carmen
authors.initials: C
authors.lastname: Limban
authors.forename: Alexandru Vasile
authors.initials: AV
authors.lastname: Missir
authors.forename: Khairi Mustafa Salem
authors.initials: KM
authors.lastname: Fahelelbom
authors.forename: Moawia Mohammad
authors.initials: MM
authors.lastname: Al-Tabakha
authors.forename: Miron Teodor
authors.initials: MT
authors.lastname: Caproiu
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced / Q000453:epidemiology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D001549:Benzamides; D002351:Carrageenan; D015232:Dinoprostone; D007213:Indomethacin
keywords: N-phenylcarbamothioylbenzamides; PGE2; gastric ulcer; indomethacin; inhibitory properties; ulcerogenic
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