Synthesis of Linear and Cyclic Disulfide Heptapeptides of Longicalycinin A and Evaluation of Toxicity on Cancerous Cells HepG2 and HT-29

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-29using 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide reagent in mtt assay.the synthetic analogues showed a relative good activity against cell lines of hepg2 and ht-29 with ic_µ50 values from 10.33µg/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.