Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity

Khwaja Fawad¹, Nazar UI Islam², Fazal Subhan¹ , Muhammad Shahid¹, Gowhar Ali¹, Faiz-Ur Rahman³, Wajahat Mahmood⁴, Nisar Ahmad¹

¹Department of Pharmacy, University of Peshawar, Peshawar 25120; ²Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan; ³Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China; ⁴Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.

For correspondence:- Fazal Subhan Email: fazal_subhan@upesh.edu.pk Tel:+9291216750

Accepted: 19 October 2017 Published: 31 January 2018

Citation: Fawad K, Islam NU, Subhan F, Shahid M, Ali G, Rahman F, et al. Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity. Trop J Pharm Res 2018; 17(1):53-63 doi: 10.4314/tjpr.v17i1.9

© 2018 The authors.
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Abstract

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.

Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5-bis(pyrrolidinomethyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using well-known testing paradigms. Aspirin served as reference standard.

Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p < 0.01, p < 0.001), 20 and 40 mg/kg (p < 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p < 0.05, p < 0.001), 100 and 150 mg/kg (1 - 5 h, p < 0.05, p < 0.01, p < 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p < 0.05, p < 0.01, p < 0.001), 1 and 1.5 h (p < 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.

Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and anti-inflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings

Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5-Bis(pyrrolidinomethyl)hydroquinone, Anti-inflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicit