Synthesis and Bioactivity of Novel Pyrrolino[3′,4′-d]isoxazole Derivatives Containing Acridinyl

Thirteen novel pyrrolino[3',4'-d]isoxazol derivatives were synthesized through 1,3-dipolar cycloaddition reaction of N-arylmaleimide with alpha-chloro-9-acridinylformoxime or N-(N,N-dimethylanilin)-C-(9-acridinyl)nitrone in the presence of triethylamine. These compounds include 3-(9-acridinyl)-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino[3',4'-d]isoxazoline derivatives 3a similar to 3f and 2-(N,N-dimethylanilin)-3-(9-acridinyl)-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino[3',4'-d]isoxazolidine derivatives 4a similar to 4g. All the compounds were identified by H-1 NMR, IR spectra and elemental analysis. The bioactivities of compounds 3 and 4 were evaluated by preliminary bioassay and they exhibited different extent of Leucocythemia activities against Human HL-60. At the test concentration of 10 mu mol/L, the inhibition activities were in the range of 0 similar to 35%, which is lower than IC50. Compounds 3f and 4g showed Cdc25A (Cell division cycle 25A) inhibition activity of 50.90% and 51.22% respectively at the test concentration of 20 mu g/mL.