New 3-(Dibenzyloxyphosphoryl)isoxazolidine Conjugates of N1-Benzylated Quinazoline-2,4-diones as Potential Cytotoxic Agents against Cancer Cell Lines.

In this study, a new series of and 5-substituted-3-(dibenzyloxyphosphoryl)isoxazolidines - were synthesized by the 1,3-dipolar cycloaddition reaction of -benzyl--(dibenzyloxyphosphoryl)nitrone and selected -allyl--benzylquinazoline-2,4-diones. All the obtained -isoxazolidines - and the samples enriched in respective -isomers were evaluated for anticancer activity against three tumor cell lines. All the tested compounds exhibited high activity against the prostate cancer cell line (PC-3). Isoxazolidines - and - and diastereoisomeric mixtures of isoxazolidines enriched in -isomer using HPLC, namely -/- (97:3) and -/- (90:10), showed the highest antiproliferative properties towards the PC-3 cell line (IC = 9.84 ± 3.69-12.67 ± 3.45 μM). For the most active compounds, induction apoptosis tests and an evaluation of toxicity were conducted. Isoxazolidine - showed the highest induction of apoptosis. Moreover, the most active compounds turned out safe in vitro as none affected the cell viability in the HEK293, HepG2, and HSF cellular models at all the tested concentrations. The results indicated isoxazolidine - as a promising new lead structure in the search for effective anticancer drugs.