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

摘要

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.