Ontology highlight
ABSTRACT:
SUBMITTER: Banerjee S
PROVIDER: S-EPMC5912893 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Banerjee Souvik S Arnst Kinsie E KE Wang Yuxi Y Kumar Gyanendra G Deng Shanshan S Yang Lei L Li Guo-Bo GB Yang Jinliang J White Stephen W SW Li Wei W Miller Duane D DD
Journal of medicinal chemistry 20180212 4
We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compounds in this scaffold, 4a, 4b, 6a, and 8b. These structures not only confirm their direct binding to the colchicine site in tubulin and reveal their detailed molecular interactions b ...[more]