Vale Nuno, Ferreira Abigail, Fernandes Iva, Alves Cláudia, Araújo Maria João, Mateus Nuno, Gomes Paula
UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal; Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy of University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
Bioorg Med Chem Lett. 2017 Jul 1;27(13):2898-2901. doi: 10.1016/j.bmcl.2017.04.086. Epub 2017 Apr 28.
Gemcitabine proven efficiency against a wide range of solid tumors and undergoes deamination to its inactive uridine metabolite, which underlies its low bioavailability, and tumour resistance was also associated with nucleoside transporter alterations. Hence, we have conjugated gemcitabine to cell-penetrating peptides (CPP), in an effort to both mask its aniline moiety and facilitate its delivery into cancer cells. Two CPP-drug conjugates have been synthesized and studied regarding both the time-dependent kinetics of gemcitabine release and their anti-proliferative activity on three different human cancer cell lines. Results obtained reveal a dramatic increase in the anti-proliferative activity of gemcitabine in vitro, upon conjugation with the CPPs. As such, CPP-gemcitabine conjugates emerge as promising leads for cancer therapy.
吉西他滨已被证明对多种实体瘤有效，它会脱氨生成无活性的尿苷代谢物，这是其生物利用度低的原因，而且肿瘤耐药性也与核苷转运体改变有关。因此，我们将吉西他滨与细胞穿透肽（CPP）偶联，旨在既掩盖其苯胺部分，又促进其进入癌细胞。我们合成了两种CPP-药物偶联物，并研究了吉西他滨释放的时间依赖性动力学及其对三种不同人类癌细胞系的抗增殖活性。所得结果表明，与CPP偶联后，吉西他滨在体外的抗增殖活性显著增加。因此，CPP-吉西他滨偶联物有望成为癌症治疗的先导药物。
