Deconstruction of Desacetamidocolchicine's B Ring Reveals a Class 3 Atropisomeric AC Ring with Tubulin Binding Properties.

ABSTRACT: Colchicine is one of the oldest known microtubule-targeting agents and also represents a classic example of axial chirality and atropisomerism in medicine. This is because colchicine's axially chiral methoxytropone-trimethoxybenzene (called the AC ring) is directly responsible for tubulin binding and is thermodynamically set into the requisite aR form by a point chiral acetamido group on its B ring. Indeed, desacetamidocolchicine (DAAC), a colchicine analogue without the acetamido group, racemizes within minutes. Herein, we describe the synthesis as well as physical and biological characterization of a series of AC ring-containing molecules that represent B-ring further deconstructed variants of DAAC. These studies revealed a novel analogue with an AC ring that is highly stable to e

SUBMITTER: Bejcek LP 

PROVIDER: S-EPMC12150326 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature