Synthesis of Linear and Cyclic Disulfide Heptapeptides of Longicalycinin A and Evaluation of Toxicity on Cancerous Cells HepG2 and HT-29
| Author | Mohammad Hassan HoushdarTehrani | en |
| Author | Abdolhamid Bamoniri | en |
| Author | Bi Bi Fatemeh Mirjalili | en |
| Author | Mohammadreza Gholibeikian | en |
| Issued Date | 2018-07-31 | en |
| Abstract | In this work, linear and cyclic disulfide heptapeptides of Longicalycinin A have been successfully synthesized by solid phase methodology with Fmoc /t-Bu and solution phase, respectively. 2-Chlorotrityl chloride resin (2-CTC) was used as a solid support. The synthesized linear disulfide analogue of Longicalycinin A was cleaved from the resin as a protected peptide. The final deprotection was performed by treatment with TFA 95% containing scavengers to achieve the deprotected linear disulfide analogue of Longicalycinin A which was characterized by different instrumental methods using LC-MS and FT-IR. Macrocyclization of deprotected linear peptide was done by an oxidating reagent. Linear and cyclic disulfide heptapeptides of Longicalycinin A were evaluated their toxic activity against cell lines of HepG2 and HT-29 using 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide reagent in MTT assay. The synthetic analogues showed a relative good activity against cell lines of HepG2 and HT-29 with IC50 values from 10.33 µg/mL to 12.45 µg/mL, in comparison to the standard drug 5-fluorouracil (5-FU). Safety profiles of the synthesized linear and cyclic disulfide analogues of Longicalycinin A were also examined on skin fibroblast cells. Between the linear and cyclic disulfide heptapeptides of Longicalycinin A, the cyclic peptide showed a considerable toxic activity on the cancerous cell lines along with a low safety result on normal cells. Therefore, the linear disulfide heptapeptide of Longicalycinin A would be encouraging to develop new anticancer agents. | en |
| DOI | https://doi.org/10.22037/ijpr.2018.2257 | en |
| Keyword | Longicalycinin A analogue | en |
| Keyword | Disulfide band | en |
| Keyword | Anticancer | en |
| Keyword | MTT assay | en |
| Keyword | Apoptosis | en |
| Publisher | Brieflands | en |
| Title | Synthesis of Linear and Cyclic Disulfide Heptapeptides of Longicalycinin A and Evaluation of Toxicity on Cancerous Cells HepG2 and HT-29 | en |
| Type | Original Article | en |