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Updated: Jul 3, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Structure-activity relationship studies on a novel class of antiproliferative agents derived from Lavendustin A. Part
Peter Nussbaumer1, Anthony P Winiski
1Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1230 Vienna, Austria. nussbaumer@lead-discovery.de
Abstract:
The potent antiproliferative agent SDZ LAP 977, which has shown efficacy in a clinical proof of concept study in actinic keratosis patients, has been previously demonstrated to block the cell cycle in mitosis. In the present study, we further explored the mode of action: SDZ LAP 977 binds to the "colchicine binding site" on tubulin and, thus, inhibits tubulin polymerization in vitro. Moreover, we established structure-activity relationships for the effect of modifications in the 2,5-dimethoxyphenyl moiety ("ring A") of the molecule on in vitro antiproliferative activity.
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