Adigun, Rasheed A. published the artcileRational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors, Computed Properties of 598-50-5, the main research area is dihydropyrimidinone quinoline hybrid plasmodium falciparum glutathione reductase inhibitor; Antimalarial agents; Dihydropyrimidinones; Molecular docking; Rational optimization; Resistance reversal.
A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesized based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a Me group to bring the mol. weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesized compounds in addition to the previously identified hits were subjected to mol. docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimized to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimized ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesized compounds indicate that these compounds possess good pharmacokinetic properties.
ChemMedChem published new progress about Antimalarials. 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, Computed Properties of 598-50-5.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem