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

In order to expand the application of fe3o4@sio2-sncl4 in the synthesis of heterocycliccompounds, in this study, we wish to report the use of one-pot three component synthesis ofpyrimido [4,5-b]quinolone derivatives (d1-d16) through reaction of 6-amino-2-(methylthio)pyrimidin-4 (3h)-one, dimedone, or 1,3-cyclohexadione and aldehydes in the presence of fe3o4@sio2-sncl4 as an efficient eco-friendly catalyst under ultrasound irradiation. the final aim of thisstudy is evaluation of antifungal activity of resulted products.synthesis of pyrimido [4,5-b]quinolin derivatives were done via three components couplingreaction of aldehyde, dimedone or 1,3-cyclohexadione and 6-amino-2-(methylthio)pyrimidin-4(3h)-one in the presence of fe3o4@sio2-sncl4 under ultrasonic irradiation in water at 60 °c. theproducts structure were studied by ft-iri, 1h nmr,ii and 13c nmrii. all the compounds werescreened for antimicrobial activity by broth microdilution methods as recommended by clsiiii.considering our results showed that compound (d13) had the most antifungal activity against c.dubliniensis, c. albicans, c. tropicalis, and c. neoformance at concentrations ranging (mic90)from 1-4 μg/ml. compounds (d9), (d10), (d14), and (d15) had significant inhibitory activitiesagainst c. dubliniensis 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-b]quinoline-4,6(3h,7h)-dione (d13) exhibited inhibitory and fungicidal activities against the testedyeasts. the specific binding mode or the binding orientation of more efficient compounds tocyp51 active site, have been also performed by molecular modeling investigations and showedthat there is a good correlation with biological test.