Synthesis of 1',2'-O-isopropylidendioxyethyl isoxazoline derivatives of natural muscarinic analogs and screening its anti-cancer and leukocyte common antigen activity on Cdc25B and CD45 in vitro

Muscimol, cycloserin and ibotenic acid which are extracted from mushroom contain isoxazole pharmacophore structure. By using muscarinic structure as a model compound and molecular recombination method, we synthesized muscarinic analogues compounds 3-(1',2'-di-O-isopropylidenedioxyethyl)-5-aryl-3a, 6a-dihydro-4,6-dioxopyrrolino3',4'-disoxazoline derivatives through 1,3-dipolar cycloaddition reaction. The structures of the target compounds were confirmed by UV-Vis, ¹H NMR, IR and elemental analysis. The drug activities of obtained compounds were screened in vitro. The pharmacophore in the structure is a potential non-covalent DNA binding, the compounds have anticancer activity and the leukocyte common antigen activity in a different extent. The preliminary results of in vitro anticancer test suggest that the inhibitory rates of compounds 3a-3o to Cdc25A phosphatase in cell division cycle ranged from 56.99%-99.94%; at the test concentration of 20 μg·mL^-1, 3f, 3h, 3i, 3m, 3o were no inhibition activity, and the rest of the compounds shows moderate to good excellent inhibition rate from 66.85% to 99.84%, even at the concentration as low as 5 μg·mL^-1. At the test concentration of 20 μg·mL^-1, except compound 3i, the rest compounds' inhibition activity of against leukocyte common antigen (LCA) CD45 protein tyrosine phosphatase A, are 63.08%-92.09%. These active compounds are potential inhibitors against Cdc25A and CD45 protein tyrosine phosphatase A, which have great application prospects in the treatment of cancers and Inflammatory and immune diseases.