Evaluation of the bioactivity of novel spiroisoxazoline typecompounds against normal and cancer cell lines.

The aim of this study was to investigate the in vitro cellular activity of novel spiroisoxazoline type compounds against normal and cancer cell lines from lung tissue (Hs888Lu), neuron-phenotypic cells (SH-SY5Y), neuroblastoma (SH-SY5Y), human histiocytic lymphoma (U937), lung cancer (A549), and leukaemia (HL-60). Our bioassay program revealed that the spiroisoxazoline type compounds show cytotoxicity only in lymphoma cell lines, which is in contrast with the pyrrolidine precursor of these spiroisoxazoline compounds, where significant cytotoxicity is seen in all normal and cancer cell lines. These data suggest a tumour-specific mechanism of action. In addition these data also show that spiroisoxazoline compounds are non-toxic in the human neuronphenotypic neuroblastoma SH-SY5Y cell line, and furthermore that they might protect cells from neurodegenerative disease.

(5R)-Ethyl 6-benzyl-8,8-dimethyl-7,9-dioxo-1-oxa-2,6-diaza-spiro-[4.4]non-2-ene-3-carboxyl-ate.

In the title compound, C(18)H(20)N(2)O(5), the pyrrolidine ring adopts an envelope conformation with the C atom bonded to the methyl groups as the flap. The dihydro-isoxazole ring is essentially planar (r.m.s. deviation = 0.041 Å) and forms a dihedral angle of 65.19 (6)° with the phenyl ring. In the crystal, neighbouring mol-ecules are linked into chains along [110] by inter-molecular C-H⋯O hydrogen bonds and weak C-H⋯π inter-actions involving the phenyl ring.

6-Benzyl-3-(1,4-dioxaspiro-[4.5]decan-2-yl)-8,8-dimethyl-1-oxa-2,6-diaza-spiro-[4.4]non-2-ene-7,9-dione.

In the title compound, C(23)H(28)N(2)O(5), the 4,5-dihydro-isoxazole ring adopts a slight envelope conformation and the dioxolane ring is in a twisted conformation. The mol-ecular structure, in the vicinity of the benzyl group, may be influenced by an intra-molecular C-H⋯O hydrogen bond which generates an S(7) ring motif. In the crystal structure, mol-ecules are linked via weak inter-molecular C-H⋯O hydrogen bonds, forming extended chains along the b axis. Further stabilization is provided by weak C-H⋯π inter-actions.