Biological evaluation and synthesis of new pyrimidine-2(1H)-ol/-thiol derivatives derived from chalcones using the solid phase microwave method

Abstract

Twenty-five new hydroxy- and methoxy-substituted 4,6-diarylpyrimidin-2(1H)-ol (20-34) and 4,6-diarylpyri\-midine-2(1H)-thiol derivatives (35-44) were synthesized from the reaction of the corresponding 1,3-diaryl-2-propene-1-one compounds (1-19) with urea or thiourea using the solid-phase microwave method. All the new synthetic compounds (20-44) were evaluated with regard to their $\alpha $-glucosidase activity. However, only compounds 22-25, 27,31,34, 35,37, and 40 exhibited a greater inhibitory effect than standard acarbose. The IC$_{50}$ values of the active compounds ranged between 2.36 and 13.34 $\mu $M. The 25 new compounds were also screened for their in vitro pancreatic lipase activity and compounds 20-27and 35-39 were found to be active. Of these compounds 26, 27, and 39 exhibited the best antilipase activities at concentrations of 0.40 $\pm $ 0.06, 0.26 $\pm $ 0.07, and 0.29 $\pm $ 0.026 $\mu $M. All the new compounds (20-44) were evaluated for their in vitro antimicrobial activity for nine test microorganisms. Compounds 20-24 and 35-39 were determined to possess a significant broad spectrum against the gram-positive bacteria Escherichia faecalis , Staphylococcus aureus , and Bacillus cereus among the tested bacterial agents. Compounds 20-24 and 35-39 exhibit the best activity against Mycobacterium smegmatis, with minimum inhibitory concentrations of 62.5--500 $\mu $g/mL, indicating their potential use as antituberculous agents. Keywords: Pyrimidine-2(1H)-ol/-thiol, chalcone, $\alpha $-glucosidase, lipase, antimicrobial, enzyme inhibition Full Text: PDF