Esfandiari Mazandaran Kiana, Mirshokraee Sayed Ahmmad, Didehban Khadijeh, Houshdar Tehrani Mohammad Hassan
Department of Chemistry, Payam noor University, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2019 Fall;18(4):1823-1830. doi: 10.22037/ijpr.2019.111721.13319.
Cancer has emerged as a leading cause of death throughout the world. Peptides are a novel class of anticancer agents that can specifically target cancer cells with low toxicity to normal tissues and thus, offer new opportunities for future cancer treatment. On the other hand, Ciprofloxacin, an antibiotic, also known to its anticancer property for enabling cell cycle arrest and creating double strand breaks in nucleic acid can trigger apoptosis of cancer cells. Thus, joining anticancer peptides with Ciprofloxacin may be good idea to get benefit of the both compounds' properties and therefore gives better anticancer agents. The aim of this study was to synthesize Ciprofloxacin- cytotoxic peptide conjugates and to investigate the anticancer activity of the resultant compounds. The conjugates were prepared by solid phase peptide synthesis technique using Fmoc strategy. Anticancer activity of these compounds was examined on three cancer cell lines, HT-29, MCF-7, MDA-MB-231 as well as skin fibroblast cells as a control, employing MTT test. Our results showed that the cytotoxic activity of the synthesized compounds against cancer cells was raised considerably without producing a high toxicity on normal cells. Moreover, Ciprofloxacin-peptide conjugates showed selectivity against different kinds of breast cancer cells, especially on those with triple negative receptors. Therefore, it can be suggested that the strategy of making Ciprofloxacin- peptide conjugates as cytotoxic agents with safety profiles on the normal cells, rise promise to find better chemotherapeutic candidates to combat cancer.
癌症已成为全球主要的死亡原因。肽是一类新型抗癌剂，能够特异性靶向癌细胞，对正常组织毒性低，从而为未来癌症治疗提供了新机遇。另一方面，抗生素环丙沙星也因其抗癌特性而闻名，它能使细胞周期停滞并在核酸中产生双链断裂，进而触发癌细胞凋亡。因此，将抗癌肽与环丙沙星结合可能是个好主意，这样可以利用两种化合物的特性，从而获得更好的抗癌剂。本研究的目的是合成环丙沙星 - 细胞毒性肽缀合物，并研究所得化合物的抗癌活性。缀合物通过使用Fmoc策略的固相肽合成技术制备。采用MTT试验，在三种癌细胞系HT - 29、MCF - 7、MDA - MB - 231以及作为对照的皮肤成纤维细胞上检测这些化合物的抗癌活性。我们的结果表明，合成化合物对癌细胞的细胞毒性活性显著提高，同时对正常细胞不会产生高毒性。此外，环丙沙星 - 肽缀合物对不同类型的乳腺癌细胞表现出选择性，尤其是对那些具有三阴性受体的细胞。因此，可以认为将环丙沙星 - 肽缀合物制备成对正常细胞具有安全性的细胞毒性剂的策略，有望找到更好的抗癌化疗候选药物。
