SYNTHESIS, CONFORMATION, AND BIOLOGICAL ACTIVITIES OF A DES-A-RING ANALOG OF 18-DEOXY-APLOG-1, A SIMPLIFIED ANALOG OF DEBROMOAPLYSIATOXIN

摘要

10-Me-Aplog-1 as a simplified analog of tumor-promoting debromoaplysiatoxin and a potent activator of protein kinase C (PKC) is a promising chemotherapeutic agent. In this study, we synthesized a des-A-ring analog (4) of 18-deoxy-aplog-1 as a synthetically-accessible analog. Compound 4 retained the conformation of the PKC-recognition part of aplogs. Moderate affinity for conventional PKC isozymes (α, β, γ) and anti-proliferative activity against NCI-H460 (lung) and MKN45 (stomach) human cancer cell lines were observed. The results suggest that 4 could serve as a lead compound for the development of conventional PKC isozyme-selective chemotherapeutic agents.