New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition

• Published in: Bioorganic chemistry Vol. 92; p. 103218
• Main Authors: Abdelgawad, Mohamed A., Bakr, Rania B., Ahmad, Waqas, Al-Sanea, Mohammad M., Elshemy, Heba A.H.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2019
• Subjects: Antioxidant; Benzimidazole; Benzoxazole; COXs; Cytotoxicity; COXs; Cytotoxicity; Antioxidant; Benzimidazole; Benzoxazole
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103218

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•The new intermediates new 6a&b and the target new pyrimidines 7a&b were designed and prepared.•The structure of new targets was proved using NMR, IR and elemental analysis.•The cytotoxicity, antioxidant, phospholipase A2-V and cyclooxygenases inhibitory activities of 7a&b were evaluated.•The docking of 7a&b was made to confirm the mechanism of action.
To enhance the cytotoxicity of benzimidazole and/or benzoxazole core, the benzimidazole/benzoxazole azo-pyrimidine were synthesized through diazo-coupling of 3-aminophenybenzimidazole (6a) or 3-aminophenylbenzoxazole (6b) with diethyl malonate. The new azo-molanates 6a&b mixed with urea in sodium ethoxide to afford the benzimidazolo/benzoxazolopyrimidine 7a&b. The structure elucidation of new synthesized targets was proved using spectroscopic techniques NMR, IR and elemental analysis. The cytoxicity screening had been carried out against five cancer cell lines: prostate cancer (PC-3), lung cancer (A-549), breast cancer (MCF-7), pancreas cancer (PaCa-2) and colon cancer (HT-29). Furthermore, the antioxidant activity, phospholipase A2-V and cyclooxygenases inhibitory activities of the target compounds 7a&b were evaluated and the new compounds showed potent activity (cytotoxicity IC50 range from 4.3 to 9.2 µm, antioxidant activity from 40% to 80%, COXs or LOX inhibitory activity from 1.92 µM to 8.21 µM). The docking of 7a&b was made to confirm the mechanism of action.