Synthesis And Biological Activity Of Aryl Nitrogen Mustard Derivatives

Nitrogen mustard, DNA-targeted alkylating agents, with N, N-bis(2-cholorethyl) amine as the pharmacophore, play an important role in current cancer chemotheraphy. In this paper, the recent progress in the synthesis of new nitrogen mustard derivatives is reviewed. Twelve novel target compounds including seven intermediates were prepared, and the structures of these compounds were characterized by 1HNMR, 13CNMR, ESI-MS and elemental analysis. We also tested the in vitro anti-tumor activities of these compounds and the interaction with Herring Sperm DNA.Part 1 IntroductionIn this part, we briefly introduced the commercial nitrogen mustard agents, and the related anti-tumor mechanism. Recent study and prospect of nitrogen mustard derivatives were also summarized.Part 2 Synthesis of Two Kinds of Nitrogen Mustard Derivatives1 Synthesis of Carbamate Nitrogen Mustard Derivatives 2 Synthesis of Benzoic Acid Nitrogen Mustard DerivativesPart 3 Biological EvaluationAll the target compounds, together with intermediate 4, 10 and the commercial drugs Melphalan, were tested in vitro for their inhibition on three kinds of cancer cells: B16, K562 and CHO by MTT methods. The results demonstrated that compounds 6c,6e and 11c possessed higher activity than the reference compound 4 or 10, and were similar to the commercial drug Melphalan in the certain scope of concentrations. The preliminary fluorescence spectra of compound 6c indicated that 6c can not displace the EB, the interaction of 6c with DNA-EB resembled that of nonionic surfactant.