PP+-CPI-613衍生物的设计、合成及抗肿瘤活性研究

PI-613 is a novel mitochondrial metabolic inhibitor that can block mitochondrial energy metabolism, thereby inducing various tumor cell death. However, the poor activity of the compound limits its clinical application. In this work, TPP+-CPI 613 conjugates were constructed using the mitochondrial targeting group TPP+, and CPI-613 was selectively delivered into mitochondria to increase its concentration at the target site, thereby enhancing its anti-tumor activity. First, CPI-613 and 10-bromo-1-decanol undergo an esterification reaction to generate compound 3, which is then refluxed with triphenylphosphine derivatives (4-8) in acetonitrile to obtain five novel TPP+-CPI 613 derivatives (9-13), whose structures have been confirmed by NMR. Next, the antiproliferative ability of derivative 9-13 was determined using the MTT assay. Results suggested that compound 9 exhibited good anti-tumor activity (IC50 = 0.20 μM, A375)and low cytotoxicity (IC50 = 2.11 μM, HUVEC).