Docking, Synthesis and Evaluation of the Antifungal Activity of Pyrimido [4,5-b]quinolins.

In order to expand the application of FeO@SiO-SnCl in the synthesis of heterocyclic compounds, in this study, we wish to report the use of one-pot three component synthesis of pyrimido [4,5-]quinolone derivatives ( ) through reaction of 6-amino-2-(methylthio)pyrimidin-4 (3)-one, dimedone, or 1,3-cyclohexadione and aldehydes in the presence of FeO@SiO-SnCl as an efficient eco-friendly catalyst under ultrasound irradiation. The final aim of this study is evaluation of antifungal activity of resulted products. Synthesis of pyrimido [4,5-]quinolin derivatives were done three components coupling reaction of aldehyde, dimedone or 1,3-cyclohexadione and 6-amino-2-(methylthio)pyrimidin-4 (3)-one in the presence of FeO@SiO-SnCl under ultrasonic irradiation in water at 60 °C. The products structure were studied by FT-IR, H NMR, and C NMR. All the compounds were screened for antimicrobial activity by broth microdilution methods as recommended by CLSI. Considering our results showed that compound ( ) had the most antifungal activity against , , and at concentrations ranging (MIC90) from 1-4 μg/mL. Compounds ( ), ( ), ( ), and ( ) had significant inhibitory activities against at concentrations ranging (MIC90) from 4-8 μg/mL, respectively. 5-(3,4-dihydroxyphenyl)-8,8-dimethyl-2-(methylthio)-5,8,9,10-tetrahydropyrimido[4,5-]quinoline-4,6(3,7)-dione ( ) exhibited inhibitory and fungicidal activities against the tested yeasts. The specific binding mode or the binding orientation of more efficient compounds to CYP51 active site, have been also performed by molecular modeling investigations and showed that there is a good correlation with biological test.