Bioactivity-Driven Synthesis of the Marine Natural Product Naamidine J and Its Derivatives as Potential Tumor Immunological Agents by Inhibiting Programmed Death-Ligand 1
Pan-Pan Fu, Qun Wang, Qing Zhang, Yang Jin, Jin Liu, Kaixian Chen, Yue‐Wei Guo, Sanhong Liu, Xu‐Wen Li
Abstract
The total synthesis of the marine natural product naamidine J and a rapid structure modification toward its derivatives were achieved on the basis of several rounds of structure-relationship analyses of their tumor immunological activities. These compounds were tested for programmed death-ligand 1 (PD-L1) protein expression in human colorectal adenocarcinoma RKO cells. Among them, compound 11c was found to efficiently suppress constitutive PD-L1 expression in RKO cells with low toxicity and further exerted its antitumor effect in MC38 tumor-bearing C57BL/6 mice by reducing PD-L1 expression and enhancing tumor-infiltrating T-cell immunity. This research work may provide insight for the discovery of new marine natural product-derived tumor immunological drug leads.