Anticancer potential of aminomethylidene-diazinanes I. Synthesis of arylaminomethylidene of diazinetriones and its cytotoxic effects tested in glioblastoma cells

Abstract

Diazinane and aryl moieties with vinylamine linkers were synthesized to investigate the importance of their structural variations as potential anti-glioblastoma agents. Structural variations incorporated on to the diazinane moiety included oxa and thio derivatives, each with a variety of nitrogen-bound substituents. The size and shape of the aromatic moiety was varied, with the final variation introducing two carbonyl groups, yielding a substituted anthraquinone. Readily available diazinanes and aryl amines were used asan advantageous foundation. Several parameters were calculated whilst engineering these compounds, including: ClogP, molecular polarizability, polar surface area, minimal molecular projected area, and pKa. In addition, a simple and efficient procedure was developed to synthesize these compounds. It was demonstrated that a vinylamine with 1,3-diazinane-2,4,6-trione and 1-anthraquinone moiety is the most promising drug candidate causing almost 70% of LN229 tumor cell death at 1µg/ml. In addition, its molecular polarizability, polar surface area and minimal molecular projected area indicate a possible potential of this molecule for crossing BBB.