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The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells

Mohammad Hassan Houshdar Tehrani1, Abdolhamid Bamoniri2, Mohammadreza Gholibeikian2

  • 1Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Iranian Journal of Basic Medical Sciences
|January 27, 2018
PubMed
Abstract

Insights

New anticancer peptide analogues of carnosine show significant cytotoxicity against cancer cells. These compounds, particularly cyclic analogues, offer potential as safer, more effective cancer treatment agents.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Cancer is a leading global cause of mortality, with conventional therapies often causing severe side effects.
  • Naturally derived compounds, such as anticancer peptides, present an opportunity for targeted cancer treatment with improved safety profiles.
  • Carnosine, a natural dipeptide, exhibits diverse biological activities, including antioxidant, anti-senescence, anti-inflammatory, and anticancer properties.

Purpose of the Study:

  • To synthesize novel peptide analogues of carnosine.
  • To evaluate the cytotoxic activity of these analogues against cancer cell lines.
  • To identify potential new anticancer agents with enhanced efficacy and safety.

Main Methods:

  • Solid-phase peptide synthesis was employed to create carnosine analogues.
  • Cytotoxic activity was assessed using MTT and lactate dehydrogenase (LDH) assays.
  • Flow cytometry analysis was performed to evaluate cellular effects.

Main Results:

  • Synthesized linear and cyclic carnosine analogues demonstrated significant cytotoxicity against HepG2 and HT-29 cancer cell lines.
  • The mean IC50 values ranged from 9.81 to 16.23 µg/ml.
  • Compounds 1c, 3c, and 6b exhibited notable toxic activity against the tested cancer cell lines.

Conclusions:

  • Cyclic carnosine analogues, specifically those with His-β-Ala-Pro-β-Ala-His (1c) and β-Ala-His-Pro-His-β-Ala (3c) sequences, showed superior cytotoxic activity compared to carnosine.
  • These analogues represent promising candidates for the development of novel anticancer therapeutics.
  • The mechanism of action is suggested to involve the induction of cancer cell apoptosis.
Keywords:
Anticancer agentsCarnosine analoguesCytotoxicityFlow cytometryMTT assayPeptide synthesis

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