The Synthesis of Conjugated Peptides Containing Triazole and Quinolone-3-Carboxamide Moieties Designed as Anticancer Agents.

Background: Cancer is a major health concern in human populations worldwide, and due to its causes being multi-factorial, it is not easily curable. Many attempts have been made to tackle this disease in hopes of finding effective anticancer agents which are not harmful to healthy tissues. Peptides with several medicinal activities have been shown to be good candidates as anticancer agents to replace common classic anticancer drugs. Peptides in conjugation with either biologically active heterocyclic compounds or anticancer drugs may result in new molecules compiling the biological benefits of both individual compounds within a unit structure. Objective: In this study some triazole-peptide conjugates as well as ciprofloxacin-peptide conjugates were designed, synthesized, and their anticancer activities evaluated. A normal skin cell line, NIH3, was also employed to determine the safety profiles of these conjugates. Materials and Methods: Two peptides; YIGSR and LSGNK were synthesized by the solid phase peptide synthesis (SPPS) method using Wang resin. Cell viability was examined by employing the MTT assay. To determine the cytotoxicity of the triazole and ciprofloxacin conjugates, two human cancer cell lines were employed; HepG2 (human liver cancer cell line) and LNCaP (human prostatic carcinoma cell line). A human skin fibroblast cell line was also included for comparison. Results: MTT results showed that all the compounds could inhibit the viability of cancerous cells in a concentration- dependent manner. Conclusions: The results showed that these peptide conjugates are toxic against the aforementioned cancerous cells and thus may raise a hope for finding new anticancer agents made by such strategy in the near future.

Design and Synthesis of Novel Triazole-based Peptide Analogues as Anticancer Agents.

Cancer disease is a great concern in the worldwide public health and current treatments do not give satisfactory results, so, developing novel therapeutic agents to combat cancer is highly demanded. Nowadays, anticancer peptides (ACPs) are becoming promising anticancer drug candidates. This is due to several advantages inherited in peptide molecules, such as being usually with small size, high activity, low immunogenicity, good biocompatibility, diversity of sequence, and more modification sites for functionalization. To get benefit of these merits, in this work, we synthesized a new series of triazole- based analogues with peptide scaffold by employing click chemistry and evaluated their anticancer activities against breast, colon cancer cell lines as well as fibroblast cells using MTT assay. Our results suggest that peptide scaffolds containing 1H-1, 2, 3-triazole ring group are toxic against colon and breast cancer cells viability, and this effect was more pronounced on MDA-MB-231 cells compared with MCF-7 breast cells. As a conclusion, these designed peptide analogues may be good and safe candidates as future anticancer agents.