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

## TL;DR

Researchers synthesized a phorbazole-like compound called B1 that shows strong anti-cancer effects, particularly against leukemia cells.

## Contribution

The study introduces an efficient synthesis method for phorbazole analogs and identifies B1 as a multi-kinase inhibitor with anti-AML activity.

## Key findings

- B1 exhibits nanomolar cytotoxicity against MV4-11 leukemia cells.
- B1 induces G0/G1 arrest and apoptosis by downregulating cyclin D1/CDK6.
- B1 shows anti-angiogenic activity by inhibiting endothelial network formation and migration.

## Abstract

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 analog B1. B1 showed 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, B1 also potently inhibited endothelial network formation and migration, demonstrating anti-angiogenic activity. This work provides an efficient synthetic strategy and identifies B1 as a promising dual-function anticancer lead compound.