Synthesis And Structural Analysis Of The Antitumor Compounds 3-Benzyloxyhydantoin Derivatives

Synthesis and structural analysis of the antitumor compounds 3-benzyloxy hydantoin derivatives have been mainly studied in this paper. Meanwhile, the hydantoin derivatives synthesized in experiment were also determined their anti-tumor activities in vitro to explore their anti-tumor effect against murine leukemia cell line L1210, human leukemia cell line K562 and human laryngreal carcinoma cell line HEP-2. Furthermore, we have preliminarily analyzed the structure and activity relation of target compounds basing on their anti-tumor activities.The primary coverage of the paper is as following:Firstly, an integrated introduction to hydantoin and hydantoin derivatives is reviewed, which involve the history research、property、natural product、synthesis and application of hydantoin derivatives.Secondly, we successfully devised a new synthetic pathway to synthesis the 3-benzyloxy hydantoin derivatives through review of literature. Unfortunately, the compounds 23,24 and 28 under the same condition did not give the hydantoin scaffold, but instead, afforded the hydroxyure derivatives. Nevertheless, these compounds would be converted into hydantoin ring efficiently under the basic condition. Finally, we obtained 28 hydantoin derivatives, which four of them (compound 1、8、15 and 22) were reported and others were novel compounds by CA inquiry. Of course, the chemical structures of all compounds were confirmed by IR, MS,1H NMR and 13C NMR spectra. At the same time, studies on X-ray diffraction analysis of target compound were performed, and we also investigated the spatial structure of hydantoin derivatives, then the crystal and experimental data were analyzed and discussed.Thirdly, proceeding from IR、MS、1H-NMR and 13C-NMR of target compound, we analyzed the characteristics of them separately and combined with the message existing in the IR, MS,1H NMR and 13C NMR spectra to make comprehensive analysis of target compound.Fourthly, the obtained hydantoin derivatives were evaluated their anti-tumor activities in vitro to explore their anti-tumor effect against murine leukemia cell line L1210 human leukemia cell line K562 and human laryngreal carcinoma cell line HEP-2. The experimental results indicated that some of the tested compounds were more efficient to inhibit the growth of tumor cells comparing with positive control drug hydroxyurea. To our surprise, the anti-tumor activities against L1210 of compounds 16 (IC50=42.56μmol/l)、21(IC50=35.61μmol/l)、24(IC50=34.61μmol/l)、26(IC5o=53.04μmol/l) and 28(IC5o=55.93μmol/l) were more prominent than hydroxyurea(IC5o=216.70μmol/1), and the compound 6(IC5o=47.8Oμmol/1)、9(IC50 =42.37μmol/1)、12(IC5o=56.63μmol/1) and 23 (IC50=39.60μmol/l) also exhibited excellent activity against K562 comparing with hydroxyurea(IC5o=72.70μmol/l).What is more, the anti-tumor affect against HEP-2 of compounds 8 (IC50 =0.47μmol/l).17(IC50=1.51μmol/l),19(IC50=0.95μmol/l)、20(IC50=0.41μmol/l) and 27(IC50=0.10μmol/l) were significantly higer than hydroxyurea (IC5o=2352.0μmol/l). In the end, we have preliminarily analyzed the structure and activity relation of target compounds basing on their anti-tumor activities.