Cancer has emerged as the main cause of the highest rate of mortality in the world. Drugs used in cancer, although, show some beneficial effects on cancerous organs, demonstrate side effects on other normal tissues. On the other hand, anticancer peptides, being effective on target tissues, should be safe and less harmful on healthy organs, since peptides have several advantages, i.e., high activity, specificity, affinity, being less immunogenic and not accumulate in the body. In the present work, analogues of Longicalcynin A, a naturally occurring anticancer cyclopeptide, were synthesized and evaluated their cytotoxicity in order to gain information from structure-activity relationships of the such cyclopeptides which may lead to find novel and safer anticancer peptide compound(s) to be used in clinic. Peptides were prepared by the solid-phase peptide synthesis method using trityl-resin. Peptide cyclization was performed in liquid phase. To study anticancer activity of the peptide analogues of Longicalycinin A, several methods including MTT, flow cytometry analysis and Lysosomal membrane integrity assay were employed using two cell lines HepG2 and HT-29. Fibroblast cells were used to control the safety of the synthesized cyclopeptides on normal cells. Two cyclopeptides 11 and 17 with the sequences of cyclo-(Thr-Val-Pro-Phe-Ala) and cyclo-(Phe-Ser-Pro-Phe-Ala), respectively were cytotoxic against the colon as well as hepatic cancer cells with safety profile against fibroblast cells, probably with the mechanism of apoptosis as lysosomal membrane integrity damaged. These cyclopeptides showed to be more favorable compounds better than Longicalycinin A and good candidates to develop cyclopeptides as anticancer agents.

中文翻译：

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Longicalcynin A类似物作为抗癌环肽的构效关系研究。

癌症已成为世界上死亡率最高的主要原因。尽管用于癌症的药物对癌性器官显示出某些有益作用，但对其他正常组织却显示出副作用。另一方面，对靶组织有效的抗癌肽应该是安全的，并且对健康器官的危害较小，因为该肽具有许多优势，即高活性，特异性，亲和性，免疫原性较低并且不会在体内积聚。在本工作中，合成了Longicalcynin A（一种天然存在的抗癌环肽）类似物，并评估了其细胞毒性，以便从此类环肽的结构活性关系中获得信息，从而可能找到新颖且更安全的抗癌肽化合物用于临床。使用三苯甲基树脂通过固相肽合成方法制备肽。在液相中进行肽环化。为了研究龙霉素A的肽类似物的抗癌活性，使用了两种细胞系HepG2和HT-29，采用了MTT，流式细胞术分析和溶酶体膜完整性测定等几种方法。成纤维细胞被用来控制合成的环肽在正常细胞上的安全性。具有环-（Thr-Val-Pro-Phe-Ala）和环-（Phe-Ser-Pro-Phe-Ala）序列的两个环肽11和17对结肠和肝癌细胞具有细胞毒性。安全性针对成纤维细胞，可能与溶酶体膜完整性受损的凋亡机制有关。