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In vivo effects of a selected thiourea derivative 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) against nociception, inflammation and gastric ulcerogenicity: Biochemical, histopathological and in silico approaches - 27/04/24

Doi : 10.1016/j.biopha.2024.116544 
Gowhar Ali a, , Farrah Deeba a, Umer Rashid b, Aman Ullah a, Hammad Ullah c, , Inayat Ali Khan d, Syed Ishtiaq Khan e, Amin Badshah f, Muhammad Arif Khan g, Muhammad Ayaz g, , Maria Daglia c, h
a Department of Pharmacy, University of Peshawar, Peshawar, Pakistan 
b Department of Chemistry, COMSATS University Islamabad, Abbottabad 22060, Pakistan 
c Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Naples 80131, Italy 
d Department of Chemistry, School of Natural Sciences (SNS), National University of Sciences and Technology (NUST), H-12 Campus, Islamabad 44000, Pakistan 
e Superintending Chemist, Geological Survey of Pakistan, Sariab Road, Quetta 87550, Pakistan 
f Department of Chemistry, Quaid-e-Azam University Islamabad, 45320, Pakistan 
g Department of Pharmacy, University of Malakand, Dir (L), Chakdara, Khyber Pakhtunkhwa 18000, Pakistan 
h International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China 

Corresponding authors.

Abstract

The current study was designed to investigate the potential of a synthetic therapeutic agent for better management of pain and inflammation, exhibiting minimal to non-existent ulcerogenic effects. The effect of 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea was assessed through model systems of nociception and anti-inflammatory activities in mice. In addition, the ulcerogenic potential was evaluated in rats using the NSAID-induced pyloric ligation model, followed by histopathological and biochemical analysis. The test was conducted on eight groups of albino rats, comprising of group I (normal saline), groups II and III (aspirin® at doses of 100 mg/kg and 150 mg/kg, respectively), groups IV and V (indomethacin at doses of 100 mg/kg and 150 mg/kg, respectively), and groups VI, VII, and VIII (lead-compound at 15 mg/kg, 30 mg/kg and 45 mg/kg doses, respectively). Furthermore, molecular docking analyses were performed to predict potential molecular target site interactions. The results showed that the lead-compound, administered at doses of 15, 30, and 45 mg/kg, yielded significant reductions in chemically and thermally induced nociceptive pain, aligning with the levels observed for aspirin® and tramadol. The compound also effectively suppressed inflammatory response in the carrageenan-induced paw edema model. As for the ulcerogenic effects, the compound groups displayed no considerable alterations compared to the aspirin® and indomethacin groups, which displayed substantial increases in ulcer scores, total acidity, free acidity, and gastric juice volume, and a decrease in gastric juice pH. In conclusion, these findings suggest that our test compound exhibits potent antinociceptive, anti-inflammatory properties and is devoid of ulcerogenic effects.

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Highlights

A selected synthetic compound, 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea, was tested in vivo and in silico.
1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea significantly inhibited chemically and thermally induced nociceptive pain.
The results of the ulcerogenic study suggest that the test compound has a much lower propensity to induce gastric ulcers.
Docking studies indicated noteworthy interactions between the test compound and target receptors.
The test compound may possess therapeutic effectiveness in treating pain and inflammation without inducing ulcerogenicity.

El texto completo de este artículo está disponible en PDF.

Abbreviations : BSA, COX, GABA, GI, MOE, NaOH, NSAIDs, PDB, PTZ, RMSD, SAIDs, TCA

Keywords : 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea, Inflammation, Nociception, NSAIDs, Ulcer


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Vol 174

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