The present work describes the synthesis, characterization, and anticancer properties of c(Lys-Pro), P1; c(Orn-Pro), P2; and conjugates PA-c(Lys-Pro), C1; PA-c(Orn-Pro), C2; EPA-c(Lys-Pro), C3; and EPA-c(Orn-Pro), C4. Among all, conjugate C4 displays potent anticancer activity with IC₅₀ 1.3 μM in MDA-MB-231, 3.5 μM in PC-3, 8.9 μM in MCF-7, and 9.6 μM in Miapaca-2 cancer cells. In addition, C4 downregulates the expression of MDM2 and abrogates the cancer cell invasion/metastasis. Through knock-down of MDM2, we demonstrate that this abrogation of metastasis by C4 is primarily MDM2 dependent. Furthermore, the animal studies underscore the antitumor as well as antimetastatic potential of C4in vivo in breast cancer model at a safe and tolerable dose of 20 mg/kg.

中文翻译：

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环二肽c（Orn-Pro）与4-乙基哌酸结合可通过调节MDM2消除癌细胞的转移

本工作描述了c（Lys-Pro），P1的合成，表征和抗癌特性。c（Orn-Pro），P2；和共轭PA-c（Lys-Pro），C1 ; PA-c（Orn-Pro），C2；EPA-c（Lys-Pro），C3；和EPA-c（Orn-Pro），C4。其中，缀合物C4具有有效的抗癌活性，IC ₅₀在MDA-MB-231中为1.3μM，在PC-3中为3.5μM，在MCF-7中为8.9μM，在Miapaca-2癌细胞中为9.6μM。此外，C4下调MDM2的表达并消除癌细胞的侵袭/转移。通过敲低MDM2，我们证明了C4消除了这种转移主要取决于MDM2。此外，动物研究强调以安全且可耐受的20 mg / kg剂量在乳腺癌模型中体内C4的抗肿瘤和抗转移潜力。