Maytansinol derivatives: side reactions as a chance for new tubulin binders.

Maytansinol is avaluable precursor fro the preparation of maytansine derivatives (known as maytansinoids). Inspired by its intriguing structure and their success in targeted cancer therapy, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives, bearing novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation and by determination of their crystal structures in complex with tubulin. The obtained results shed further light on the intriguing chemical behaviour of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.