Design and Synthesis of Novel cyclopeptide Derivatives as New Cytotoxic Agents

A new series of anti-cancer agents based on cyclopeptide scaffold containing methyl sulfonyl group at the para position of the C-4 phenyl ring were synthesized and their cytotoxic activities were determined against several human cancer cell lines. compounds, c Glu-Ser-Pro-Lys-PhSO2Me (1v), c Gly-Pro-Ala-Lys-PhSO2Me (2v) c Ser-Glu-Gly-Pro-Lys-PhSO2Me (3v) c Lys-Gly-Pro-Asp-PhSO2Me (4v)   c Asp-Gly-Pro-Lys-PhSO2Me (5v) were synthesized and characterized by lc-mass spectroscopy and NMR .based on the results  the most potent cytotoxic cyclicpeptide against A549 cell line was (1v) with IC50 values 3.18 µM  and the most potent cytotoxic cyclicpeptide against MCF-7 cell line was (5v) with IC50 values 2.46 µM   respectively, while most of the compounds had sufficient activity against MCF-7, HEPG-2 , HT-29 and A-549 cell lines are with mean IC50 values ranging from 2.46 to 31.44 µM. Introduction: The logical design of this study was based on the use of pharmacophoric moiety of COX-2 inhibitors with aromatic or cyclic amino acids and acidic amino acids to simulate the structure of COX-2 inhibitors. As a result, it would be appealing to COX-2 inhibitors with peptide structure which show antitumor and anti-inflammatory effects. Methods and Results: The results clearly indicated that modified cyclopeptides (1v - 5v), showed significant cytotoxic activity against all chosen cell lines. Compound (5v) showed a great anti-cancer activity against MCF-7 cell line and Compound (3v) showed a great anti-cancer activity against A549 cell line. Conclusions: In this study we synthesized 5 modified cyclopeptides by solid phase peptide synthesis approach and examined the cytotoxicity of them on 4 different cell lines. This study indicates that all synthesized compounds showed significant cytotoxicity against different cell lines specially against MCF-7 and A549 cell lines. In addition, modifications on the sequence of modified cyclopeptides had a significant influence on the cell cytotoxicity

Preparation and Characterization of Desmopressin Peptide Attached Multi-Walled Carbon Nanotube

Desmopressin, a synthetic analogue of vasopressin, has many applications in medicine including diabetes insipidus, night bedwetting, and hemophillia A. In this work, the attachment of desmopressin to multi-walled carbon nanotubes (MWCNTs), functionalized by HNO3 and H2SO4 treatment was first used to remove the unwanted catalyst from MWCNTs and meanwhile introduced carboxylic acid groups onto the surface of MWCNTs. These carboxylic groups were then used as reaction sites for the attachment of desmopressin peptide to MWCNTs. The reagents used for the attachment were oxalyl chloride and dicyclohexylcarbodiimide (DCC). The Covalent attachment of desmopressin to functionalized MWCNTs was confirmed by Fourier Transform infrared spectroscopy (FT-IR), Raman scattering, and Field Emission Scanning Electron Microscopy (FESEM).HIGHLIGHTS•The conversion of carboxylic groups to oxalyl chloride on the surface of MWCNTs.•The conversion of carboxylic groups to O-acylisourea on the surface of MWCNTs.•DCC and oxalyl chloride activate groups on MWCNTs for nucleophilic substitution.•Desmopressin is a cyclic nonapeptide with one disulfide bridge.•The Covalent attachment of desmopressin to functionalized MWCNTs

Design, Synthesis and Evaluation of Linear and Cyclic Peptide Analogues of Carnosine as Anticancer Agents

Aim Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide widely and abundantly distributed in the muscle and nervous tissues of animal species. Carnosine contains several beneficial biological properties such as antiglycating and antioxidant activities. It also contains antineoplastic effects in human cell culture as well as in animal experiments, however, the clear molecular basis of this activity has not been known yet. In the present study, in order to further examine structural basis of Carnosine for the anticancer activity, some linear and cyclic Carnosine peptide analogues were synthesized and their cytotoxicity were examined. Material and Methods  Linear and cyclic Carnosine peptide analogues were synthesized with appropriate protected amino acids and reagents using solid-phase peptide synthesis strategy, and anti-neoplastic activity of the synthesized compounds were examined on cancer cell lines of HepG2 (Human Liver Cancer Cell Line) and HT-29 (Human Colorectal Adenocarcinoma Cell Line) using MTT assay and flow cytometry analysis. Safety profile of the synthesized Carnosine analogues was also examined using skin fibroblast cells. Results  Our results showed that Carnosine analogues were toxic against HepG2 and HT-29 cell lines with a mean IC50 value 12.7 µg/mL. Flow cytometry analysis showed that such toxic activity could be, at least partly, through apoptosis induction. Conclusion  According to our experiments, in overall, compound 3b can be a good candidate for the further development of safe anticancer agents. On the other hand, cyclic peptides analogues of Carnosine, 1c and 2c, considering the properties of toxicity activities good enough on cancerous cell lines along with high safety profiles on normal skin cells, could be candidates for further works on finding anticancer agents with peptide structure giving better physicochemical properties for oral administration.   &nbsp

Design and Synthesis of Novel Tetrapeptide Analogues as New Cytotoxic Agents

New series of compounds based on a tetrapeptide scaffold containing methyl sulfonyl group at the para position of a phenyl ring were synthesized and their cytotoxic activities were examined against several human cancer cell lines including MCF-7 (breast cancer Cell Line), HepG2 (human liver cancer Cell Line), HT-29 (Human Colorectal Adenocarcinoma Cell Line) and A549 (adenocarcinomic human alveolar basal epithelial cells) using MTT assay. Based on the results, among the synthesized peptides, 5e, 5f, 1g, and 3g were the most potent cytotoxic compounds that were more toxic than the reference compound, Celecoxib, against the tested cell lines. These compounds could be candidate for finding cytotoxic agents with new peptide scaffolds which show COX-2 inhibitory activity as well. HIGHLIGHTS•A group of tetrapeptides was reported as COX-2 inhibitors with antiproliferative activity.•New tetrapeptides containing methyl sulfonyl group at the para position of a phenyl ring were synthesized.•Some of novel compounds exhibited more potent cytotoxic effect than Celecoxib as the reference

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 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

Identification of Proteins Participating in the Cisplatin Resistance Following Treatment with Cisplatin in A2780 and A2780CP Ovarian Cell Lines: Proteomics analysis of cisplatin resistance in A2780 cell line

Ovarian cancer is the most fatal gynecological cancer and the 8th most prevalent type of cancer in Iran. Chemotherapy regimen for the treatment of this type of cancer is mostly based on platinum agents and paclitaxel. The major problem during treatment with cisplatin is the appearance of acquired resistance in cancer cells in the first 6 months of therapy. Owing to inefficacy of second line regimens, it seems necessary to find out the molecular mechanisms of cisplatin resistance and find an efficient strategy against the resistant cancer cells. In this study, two ovarian cancer cell lines, A2780-sensitive and A2780CP (resistant to cisplatin) were evaluated. To acquire the protein expression profile, a culture of each line containing 1.5×107 cells was divided into the two groups of control and treatment cells. The treatment group cells were treated with cisplatin at pre-determined IC50 concentration for 6 hours. Then, the total proteins of 7×106 cells were extracted. The proteome of each group (20 μg) was used for subsequent separation of proteins by two-dimensional gel electrophoresis using 7 cm IPG strips. The results of protein pattern changes were analyzed by one-way ANOVA. At least 230 proteins were detected in each gel, from which, about 45 proteins were differentially expressed in each model of comparison. However, by considering the results of all models of analysis on the protein expression profile of two cell lines, three proteins were determined as the key players of resistance against cisplatin. HIGHLIGHTS The major problem during treatment with cisplatin is the appearance of acquired resistance in cancer cells. The cisplatin- resistant and sensitive ovarian cell lines of A2780 were evaluated in this study. Proteomics analysis was run using 2D gel electrophoresis after cisplatin treatment. Three proteins were determined as the key players of resistance against cisplatin in A2780 cell line

The Effect of Synthesized Triazole and Ciprofloxacin Conjugated Peptide Compounds on Biological systems: Biological effects of Triazole and Ciprofloxacin Conjugated Peptide.

Breast cancer is the most common cancer among women and only second in terms of cancer-related death in women. Finding new approaches to treat such cancers is critically important anti-cancer peptides (ACPs) offer the possibility of efficient-cancer drugs, and therefore, the development of drug delivery systems using ACPs as a synergism factor is an attractive strategy to address the current drawbacks of cancer therapeutics. This work investigated the cytotoxicity for a series of synthesized compounds based on triazole or ciprofloxacin conjugated peptides against T-47D breast cancerous cells and possible antibacterial effects. Wang resin was used for constructing peptide sequences on a solid support using the method of solid-phase peptide synthesis (spps) with the Fmoc strategy. Cytotoxicity of the synthesized peptide compounds was evaluated by MTT assay. The antimicrobial effect of synthesized peptide compounds was evaluated by agar well diffusion and Broth microdilution method. Most of the peptide compounds showed a cytotoxic effect toward T-47D cells. The antimicrobial effect of the peptide compounds was examined by agar well diffusion test and broth microdilution method. E. coli and S. aureus strains have shown the least amount of resistance. In the end, we suggest a new design based on these compounds and modifications to gain better anti-cancer agent