Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure-activity relationship, in vitro and in vivo evaluation as antitumor agents.

ABSTRACT: The design, synthesis, and biological evaluation of a series novel N1‑methyl pyrazolo[4,3-d]pyrimidines as inhibitors of tubulin polymerization and colchicine binding were described here. Synthesis of target compounds involved alkylation of the pyrazolo scaffold, which afforded two regioisomers. These were separated, characterized and identified with ¹H NMR and NOESY spectroscopy. All compounds, except 10, inhibited [³H]colchicine binding to tubulin, and the potent inhibition was similar to that obtained with CA-4. Compounds 9 and 11-13 strongly inhibited the polymerization of tubulin, with IC₅₀ values of 0.45, 0.42, 0.49 and 0.42 μM, respectively. Compounds 14-16 inhibited the polymerization of tubulin with IC_50s near ∼1 μM. Compounds 9, 12, 13

SUBMITTER: Islam F 

PROVIDER: S-EPMC8113149 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature