Tubulin-binding dibenz[c,e]oxepines: Part 2. Structural variation and biological evaluation as tumour vasculature disrupting agents

Abstract

5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin -heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4.

A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines

“…Furthermore, the analog structures of DO derivatives with benzene rings were found to be contributing to inhibiting microtubules in HBC cell lines (MDA-MB0-468, MCF-7, and HS578T) with a less than half-maximal inhibitory concentration (IC 50 ) values [34]. Because of the importance of the DO core as a pharmacophore, wide synthetic efforts have been made [35]. Benzo [6,7]oxepino [3,2-b]pyridine (BZOP) (Figure 1B) is an analog of DO.…”