Concise Synthesis and Biological Evaluation of a Phorbazole Analogue-B1 Identifies a Multi-Kinase Inhibitor with Anti-AML Activity
Xiang Chen, Liting Zhang, Jinqi Huang, Mingzhi Su, Yuewei Guo, Xin Jin
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.
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.
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Taxonomy
TopicsMicrobial Natural Products and Biosynthesis · Marine Sponges and Natural Products · Histone Deacetylase Inhibitors Research