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

• Published in: European journal of medicinal chemistry Vol. 45; no. 6; pp. 2689 - 2694
• Main Authors: Sarhan, Abdelwareth A.O., Al-Dhfyan, Abdullah, Al-Mozaini, Maha A., Adra, Chaker N., Aboul-Fadl, Tarek
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01-06-2010; Elsevier
• Subjects: 3-Aminothiazolo[3,2- a]benzimidazole-2-carbonitrile; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Biological and medical sciences; Cell Cycle - drug effects; Cell cycle disruption; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxic activity; G2/M phase; General aspects; Humans; Medical sciences; Nitriles - chemical synthesis; Nitriles - chemistry; Nitriles - pharmacology; Pharmacology. Drug treatments; Cell cycle disruption; G2/M phase; 3-Aminothiazolo[3,2- a]benzimidazole-2-carbonitrile; Cytotoxic activity; Apoptosis; Human; Flow cytometry; Nitrile; Cytotoxicity; 3-Aminothiazolo[3,2-a]benzimidazole-2-carbonitrile; In vitro; Biological activity; Cell line; Cell cycle; Mammary gland; Chemical synthesis; Tumor cell
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.02.025

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.
[Display omitted] 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.