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

摘要

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 $lpha $-glucosidase activity. However, only compounds 22 -25 , 27 ,31 ,34 , 35 ,37 , and 40 exhibited a greater inhibitory effect than standard acarbose. The IC$_{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 -27 and 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.