Cell cycle disruption and apoptotic activity of 3-aminothiazolo[3,2-a]benzimidazole-2-carbonitrile and its homologues

3-Aminothiazolo[3,2-a]benzimidazole-2-carbonitrile (2) was prepared and upon hydrolysis using concentrated sulfuric acid or phosphoric acid resulted in the corresponding 3-aminothiazolo[3,2-a]benzimidazole-2-carboxamide derivative (3). Cyclization of the 2 using acetic anhydride or formic acid gave the corresponding pyrimido[4′,5′:4,5]thiazolo[3,2-a]benzimidazol-4(3H)-one (5) in good yields. Acetylation of 2 with acetic anhydride in pyridine afforded N-acetylaminothiazolo[3,2-a]benzimidazole-2-carbonitrile (6). In vitro antiproliferative activities of synthesized compounds were investigated at The National Cancer Institute (NCI), USA, according to their applied protocol. Compound 6 revealed significant antiproliferative activity, however, weak activity was shown by the other derivatives. Cell cycle disruption and apoptotic activity of 6 were studied, interestingly, 6 has the ability to arrest G2/M phase and it can induce apoptosis in time dependant manner.

Among a synthesized series of aminothiazolo[3,2-a]benzimidazole derivatives N-acetylaminothiazolo[3,2-a]benzimidazole-2-carbonitrile revealed significant in vitro antiproliferative activity which attributed to its ability to arrest G2/M phase and to induce apoptosis in time dependant manner.Figure optionsDownload as PowerPoint slide