Anti-nociceptive effect of some synthesized smaller chain tripeptides and tetrapeptides in mice
The present study describes an approach to synthesize the smaller chain tripeptides and tetrapeptides and to test their antinociceptive potency in mice. Based on rational drug design using hydrophobic ratio and total net charge as descriptors, five leads were selected, viz., Met-Arg-Tyr (MRY), Met-Val-Tyr (MVY), Met-Ile-Cys-Tyr (MICY), Met-Trp-Lys-Tyr (MWKY) and Phe-Trp-Lys-Tyr (FWKY) from the subjected 65 templates and synthesized by dicyclohexyl carbodiimide coupling using polystyrene as solid support. All the synthesized compounds were purified by column chromatography and further confirmed by melting point, infrared, proton nuclear magnetic resonance and mass spectral datas. Acute toxicity studies were performed for dose selection in all the compounds using OECD guidelines 423 (Annexure 2b). Antinociceptive potency of peptides was tested in Swiss albino mice using acetic acid writhing and hot plate method. The LD50 cut-off mg/kg body weight for tripeptides (MRY, MVY) and tetrapeptides (Met-Ile-Cys-Tyr, Met-Trp-Lys-Tyr, Phe-Trp-Lys-Tyr) were found to be 500–2000 mg/kg and 200–300 mg/kg respectively. The tripeptide MVY have shown maximum antinociceptive action with an average number of writhing as 13 at 150 mg/kg body weight by writhing method, whereas the tripeptide Met-Arg-Tyr have shown maximum potency with the average reaction time of 5.75 min after 15 min at a dose of 150 mg/kg by hot plate method, which clearly indicated that the tripeptides are comparatively potent antinociceptive agents than the tetrapeptides for central neuropathic pain.
KeywordsTetrapeptides Tripeptides Acute toxicity Antinociceptive activity Drug design Met-Arg-Tyrosine
The authors remain thankful to Dr. Umakant Bajaj, Principal, KIET School of Pharmacy for the provision of laboratory facilities.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Bhargave CS (2013) Study of effect of nimesulide co-administered with calcium channel blockers on nociception, in Swiss albino mice. Int J Pharmacol Bio Sci 7(1):55–60Google Scholar
- Committee on Advancing pain research, and Education; Institute of Medicine (2011) Relieving pain in America: a blueprint for transforming prevention, care, education, and research. National Academic Press, WashingtonGoogle Scholar
- Gross JH (2010) Mass spectrometry-a textbook. Springer International, Heidelberg, 300–307Google Scholar
- Koeter HBMW (1990) The science and the art of regulatory toxicology: how to deal with alternative tests. OECD Environment Monographs, USAGoogle Scholar
- Pawar SD, Gaidhani SN, Anandan T, Lavekar GS, Kumari S, Padhi MM et al. (2011) Evaluation of anti-inflammatory, analgesic and anti-arthritic activity of yograja guggulu in laboratory animals. Int J Pharmacol Bio Sci 5(2):17–25Google Scholar
- Silverstein RM, Webster FX (2005) Spectrometric identification of organic compounds. Wiley India (P) Ltd., New DelhiGoogle Scholar
- Tegge W, Bonafe CFS, Teichmann A, Erck C (2010) Synthesis of peptides from α- and β-tubulin containing glutamic acid side chain linked oligo-glu with defined length. Int J Peptides. doi: 10.1155/2010/189396
- Wilcox NL (1994) Regulatory aspects in the US Food and drug administration: in alternative methods in toxicology. Mary Ann-Liebert Inc., USAGoogle Scholar