Concise Synthesis and Biological Evaluation of a Phorbazole Analogue-B1 Identifies a Multi-Kinase Inhibitor with Anti-AML Activity

Phorbazoles are bioactive marine alkaloids whose development is hampered by limited supply. We report a concise synthesis of the deschloro-phorbazole core via an optimized iodine-catalyzed oxazole annulation (56% yield). This route enabled efficient access to the scaffold and the preparation of analogB1.B1showed nanomolar cytotoxicity (IC50= 0.04 µM) against MV4-11 leukemia cells by inducing G0/G1 arrest (via cyclin D1/CDK6 downregulation) and apoptosis. As a multi-kinase inhibitor,B1also potently inhibited endothelial network formation and migration, demonstrating anti-angiogenic activity. This work provides an efficient synthetic strategy and identifiesB1as a promising dual-function anticancer lead compound.