The toxicity study of synthesized inverse carnosine peptide analogues on HepG۲ and HT-۲۹ cells

سال انتشار: 1397
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 144

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شناسه ملی سند علمی:

JR_IJBMS-21-1_007

تاریخ نمایه سازی: 27 مهر 1400

چکیده مقاله:

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 HepG۲ and HT-۲۹ 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 HepG۲ and HT-۲۹ cell lines with mean IC۵۰ values ranging from ۹.۸۱ to ۱۶.۲۳ µg/ml. Among the peptides, compounds ۱c, ۳c and ۶b (linear analogue of ۳c) showed a considerable toxic activity on the cancerous cell lines. Conclusion: The cyclic peptide analogues of carnosine withHis-β-Ala-­Pro-β-Ala-­His (۱c) and β-Ala-­His- Pro­-­His-­β-Ala (۳c) sequences showed cytotoxic activity on cancerous cells of HepG۲ and HT-۲۹, better than carnosine, and thus can be good candidates to develop new anticancer agents. The mechanism of cytotoxicity may be through cell apoptosis.

نویسندگان

Mohammad Hassan Houshdar Tehrani

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

Abdolhamid Bamoniri

Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran

Mohammadreza Gholibeikian

Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran

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