The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells
Objective: Cancer has risen as the main cause of diseases with the highest rate of mortality in the world. Drugs used in cancer, usually demonstrate side effects on normal tissues. On the other hand, anticancer small peptides, effective on target tissues, should be safe on healthy organs, as being n...
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doaj-34ae4754b2e749919ad327f06f056c5d2020-11-24T23:20:28ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences 2008-38662008-38742018-01-01211394610.22038/ijbms.2017.23153.58529860The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cellsMohammad Hassan Houshdar Tehrani0Abdolhamid Bamoniri1Mohammadreza Gholibeikian2Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, IranDepartment of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, IranObjective: Cancer has risen as the main cause of diseases with the highest rate of mortality in the world. Drugs used in cancer, usually demonstrate side effects on normal tissues. On the other hand, anticancer small peptides, effective on target tissues, should be safe on healthy organs, as being naturally originated compounds. In addition, they may have good pharmacokinetic properties. carnosine, a natural dipeptide, has shown many biological functions, including anti-oxidant, anti-senescence, anti-inflammatory and anticancer activities. This study, with the aim of introducing new anticancer agents with better properties, is focused on the synthesis and cytotoxic evaluation of some peptide analogues of carnosine. Materials and Methods: The cytotoxic activity of the synthesized peptides, prepared by the solid-phase peptide synthesis method, was evaluated against two cell lines of HepG2 and HT-29 using MTT assay, lactate dehydrogenase (LDH) assay and flow cytometry analysis. Results: Linear and cyclic analogues of carnosine peptide showed cytotoxicity, demonstrated by several experiments, against HepG2 and HT-29 cell lines with mean IC50 values ranging from 9.81 to 16.23 µg/ml. Among the peptides, compounds 1c, 3c and 6b (linear analogue of 3c) showed a considerable toxic activity on the cancerous cell lines. Conclusion: The cyclic peptide analogues of carnosine withHis-β-Ala-Pro-β-Ala-His (1c) and β-Ala-His- Pro-His-β-Ala (3c) sequences showed cytotoxic activity on cancerous cells of HepG2 and HT-29, better than carnosine, and thus can be good candidates to develop new anticancer agents. The mechanism of cytotoxicity may be through cell apoptosis.http://ijbms.mums.ac.ir/article_9860_33565322529d15e805cf6028ee619af0.pdfAnticancer agentsCarnosine analoguesCytotoxicityFlow cytometryPeptide synthesisMTT assay |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mohammad Hassan Houshdar Tehrani Abdolhamid Bamoniri Mohammadreza Gholibeikian |
spellingShingle |
Mohammad Hassan Houshdar Tehrani Abdolhamid Bamoniri Mohammadreza Gholibeikian The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells Iranian Journal of Basic Medical Sciences Anticancer agents Carnosine analogues Cytotoxicity Flow cytometry Peptide synthesis MTT assay |
author_facet |
Mohammad Hassan Houshdar Tehrani Abdolhamid Bamoniri Mohammadreza Gholibeikian |
author_sort |
Mohammad Hassan Houshdar Tehrani |
title |
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells |
title_short |
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells |
title_full |
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells |
title_fullStr |
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells |
title_full_unstemmed |
The toxicity study of synthesized inverse carnosine peptide analogues on HepG2 and HT-29 cells |
title_sort |
toxicity study of synthesized inverse carnosine peptide analogues on hepg2 and ht-29 cells |
publisher |
Mashhad University of Medical Sciences |
series |
Iranian Journal of Basic Medical Sciences |
issn |
2008-3866 2008-3874 |
publishDate |
2018-01-01 |
description |
Objective: Cancer has risen as the main cause of diseases with the highest rate of mortality in the world. Drugs used in cancer, usually demonstrate side effects on normal tissues. On the other hand, anticancer small peptides, effective on target tissues, should be safe on healthy organs, as being naturally originated compounds. In addition, they may have good pharmacokinetic properties. carnosine, a natural dipeptide, has shown many biological functions, including anti-oxidant, anti-senescence, anti-inflammatory and anticancer activities. This study, with the aim of introducing new anticancer agents with better properties, is focused on the synthesis and cytotoxic evaluation of some peptide analogues of carnosine. Materials and Methods: The cytotoxic activity of the synthesized peptides, prepared by the solid-phase peptide synthesis method, was evaluated against two cell lines of HepG2 and HT-29 using MTT assay, lactate dehydrogenase (LDH) assay and flow cytometry analysis. Results: Linear and cyclic analogues of carnosine peptide showed cytotoxicity, demonstrated by several experiments, against HepG2 and HT-29 cell lines with mean IC50 values ranging from 9.81 to 16.23 µg/ml. Among the peptides, compounds 1c, 3c and 6b (linear analogue of 3c) showed a considerable toxic activity on the cancerous cell lines. Conclusion: The cyclic peptide analogues of carnosine withHis-β-Ala-Pro-β-Ala-His (1c) and β-Ala-His- Pro-His-β-Ala (3c) sequences showed cytotoxic activity on cancerous cells of HepG2 and HT-29, better than carnosine, and thus can be good candidates to develop new anticancer agents. The mechanism of cytotoxicity may be through cell apoptosis. |
topic |
Anticancer agents Carnosine analogues Cytotoxicity Flow cytometry Peptide synthesis MTT assay |
url |
http://ijbms.mums.ac.ir/article_9860_33565322529d15e805cf6028ee619af0.pdf |
work_keys_str_mv |
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