Synthesis of 4-morpholino-5,8,9,10-tetrahydropyrimido[4,5–b]quinolin-6(7H)-one derivatives and in silico-in vitro evaluation of their antimalarial activity

Abstract

A novel series of 4-morpholino-5,8,9,10-tetrahydropyrimido[4,5–b]quinolin-6(7H)-one has been synthesized by an extremely effective, straightforward and clean methodology for one-pot multicomponent condensation reaction (MCRs) utilizing polyphosphoric acid as a catalyst in conjunction with acetic acid. The three-components 4-amino-6-morpholinopyrimidine, cyclohexane-1,3-dione and various aromatic aldehydes resulted in the synthesis of high-yielding compounds, to gauge their in vitro antimalarial activity toward P. falciparum 3D7 strain cultures. The compounds demonstrated outstanding inhibition with IC50 values ranging from 0.62 to 0.84 μg/mL. Compounds 3c and 3e exhibited the most significant action with IC50 values of 0.62 μg/mL which is also supported by in silico ADME and molecular docking study. These newly synthesized pyrimido[4,5–b]quinolines aim to enhance antimalarial drugs, potentially opening up new routes in pharmaceutical chemistry.

Keywords

• Morpholine
• Pyrimido[4,5–b]quinoline
• Antimalarial agents
• Plasmodium falciparum