Adamantyl-substituted ligands of colchicine binding site in tubulin: different effects on microtubule network in cancer cells

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.