Medicinal Chemistry Research

, Volume 25, Issue 12, pp 2752–2772 | Cite as

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

  • Kandasamy Nagarajan
  • Vinay Kumar
  • Parul Grover
  • Roma Ghai
  • Pritesh Kumar Rai
  • Shamshir Alam
  • Umakant Bajaj
Original Research

Abstract

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.

Keywords

Tetrapeptides Tripeptides Acute toxicity Antinociceptive activity Drug design Met-Arg-Tyrosine 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kandasamy Nagarajan
    • 1
  • Vinay Kumar
    • 2
  • Parul Grover
    • 1
  • Roma Ghai
    • 2
  • Pritesh Kumar Rai
    • 1
  • Shamshir Alam
    • 3
  • Umakant Bajaj
    • 4
  1. 1.Department of Pharmaceutical ChemistryKIET School of PharmacyGhaziabadIndia
  2. 2.Department of PharmacologyKIET School of PharmacyGhaziabadIndia
  3. 3.Department of Clinical PharmacyUnaizah College of Pharmacy, Qassim UniversityBuraydahKingdom of Saudi Arabia
  4. 4.KIET School of PharmacyGhaziabadIndia

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