Synthesis, enzyme inhibition and anticancer investigation of unsymmetrical 1,3-disubstituted ureas

Abstract

In this research work seventeen urea derivatives, including five new derivatives N-mesityl-N'-(3-methylphenyl)urea (2), N-(3-methoxyphenyl)-N'-(3-methylphenyl)urea (4), N-mesityl-N'-(4-methylphenyl)urea (6), N-(1,3-benzothiazol-2-yl)-N'-(3-methylphenyl)urea (9) and N-(2-methylphenyl)-2-oxo-1-pyrrolidinecarboxamide (15) have synthesized by reacting ortho, meta and para tolyl isocyanate with primary and secondary amines by previously reported method. We exhibited all series (1-17) to urease, β-glucuronidase and snake venom phosphodiesterase enzyme inhibition assays. The ranges of % inhibition for urease, β-glucuronidase and phosphodiesterase enzymes were 0.3-45.3, 4.9-44.9 and 1.2-46.4 % respectively. Moreover, the effect of these compounds on prostate cancer cell lines was also observed. The new compound N-(1,3-benzothiazol-2-yl)-N'-(3-methylphenyl)urea (9) showed in vitro anticancer activity with IC50 value of 78.28 ± 1.2 μM. All the compounds were characterized by state of art spectroscopic techniques.

Keywords

• amine
• β-glucuronidase
• disubstituted ureas
• isocyanate
• phospho-diesterase
• urease