Anti-nociceptive effect of some synthesized smaller chain tripeptides and tetrapeptides in mice

• Published in: Medicinal chemistry research 2016-12, Vol.25 (12), p.2752-2772
• Main Authors: Nagarajan, Kandasamy, Kumar, Vinay, Grover, Parul, Ghai, Roma, Rai, Pritesh Kumar, Alam, Shamshir, Bajaj, Umakant
• Format: Article
• Language: English
• Subjects: Acetic acid; Acute toxicity; Biochemistry; Biomedical and Life Sciences; Biomedicine; Body weight; Carbodiimide; Cell Biology; Column chromatography; Drug development; Hydrophobicity; Melting points; Neuralgia; NMR; Nuclear magnetic resonance; Original Research; Pain perception; Peptides; Pharmacology/Toxicology; Polystyrene; Polystyrene resins; Synthesis
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-016-1695-7

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 LD 50 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.