Abstract
Four novel conjugates of adamantane connected at a bridgehead position via four-bond linker to structurally different ligands interacting with colchicine binding site of tubulin were synthesized. All compounds were found to inhibit cancer cell proliferation and, notably, to promote the formation of different atypical tubulin assemblies — clusters, curly, or “entangled” microtubules. The distinction in the observed effects for conceptually equivalent structural templates can be partially explained on the basis of computer molecular modeling.
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Funding
This work was supported by Russian Fund of Fundamental Research (project no. №18-03-00524) and the German organization DAAD (German Academic Exchange Service) under the auspices of a collaborative agreement between Moscow and Rostock Universities.
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Zefirov, N.A., Evteeva, Y.A., Wobith, B. et al. Adamantyl-substituted ligands of colchicine binding site in tubulin: different effects on microtubule network in cancer cells. Struct Chem 30, 465–471 (2019). https://doi.org/10.1007/s11224-018-1219-9
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DOI: https://doi.org/10.1007/s11224-018-1219-9