Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Computational and pharmacological evaluation of stevioside derivatives for antinociceptive and anti-inflammatory potential

Sadaf Ahmad¹, Arif-ullah Khan¹, Muhammad Faheem¹ , Muhammad Shahid Iqbal², Mohammad Akbar Hossain³, Asad Ullah⁴, Shabir Ahmad⁴

¹Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; ²Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University Alkharj, Saudi Arabia; ³Department of Pharmacology and Toxicology, College of Pharmacy Al-Qura University, Makkah al Mukarramah, Saudi Arabia; ⁴Department of Pharmacology and Toxicology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.

For correspondence:- Muhammad Faheem Email: muhammad.faheem@riphah.edu.pk

Accepted: 19 July 2020 Published: 31 August 2020

Citation: Ahmad S, Khan A, Faheem M, Iqbal MS, Hossain MA, Ullah A, et al. Computational and pharmacological evaluation of stevioside derivatives for antinociceptive and anti-inflammatory potential. Trop J Pharm Res 2020; 19(8):1677-1684 doi: 10.4314/tjpr.v19i8.16

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To carry out computational and pharmacological evaluation of two stevioside derivatives in order to develop more effective candidates for analgesia and inflammation.

Methods: Primarily, compounds were docked against targets of nociception and inflammation such as cyclooxygenase-1, cyclooxygenase-2, 5-lypooxygenase 12-lypooxygenase, 15-lypooxygenase, prostaglandin synthase, leukotrienes C4 synthase, mu, kappa, and delta receptors to obtain their possible binding modes. Test compounds were then screened in animal model of nociception and inflammation.

Results: The results of docking show that IO possesses good affinity when compared to ID. IO showed two hydrogen bonds against COX-1 and COX-2. IO also demonstrated good binding against 5-LOX, 12-LOX and 15-LOX, exhibited four, one and two hydrogen bonds respectively. Against PG synthase and LTC4, both IO and ID produced moderate binding. IO also showed significant binding against opoid receptors (p < 0.05). IO and ID significantly decrease the number of writhes to 21.20 ± 2.1 and 27.0 ± 2.12 at 10 mg/kg in acetic acid mediated pain test respectively. In hot plate method, IO and ID increase the latency period of mice to 14.14 ± 0.40 and 10.50 ± 0.34 s, respectively. IO and ID significantly reduced the paw edema to 1.69 ± 0.14 and 1.94 ± 0.14 mL, respectively, in acute inflammation (p < 0.05). In chronic inflammatory model, IO and ID decreased paw volume to 3.26 ± 0.38 and 4.20 ± 0.38 mL, respectively.

Conclusion: The results show that IO is a promising candidate for further development as analgesic and anti-inflammatory agents. However, their pharmacokinetic and pharmacodynamic profiles need to be investigated.

Keywords: Computational, Stevioside, Docking, Analgesic, Anti-inflammatory