Synthesis and molecular docking study of Some 3,4-Dihydrothieno[2,3-d]pyrimidine Derivatives as Potential Antimicrobial Agents

Abstract Developing new antimicrobial agents is a good solution to overcome drug-resistance. We report the design and synthesis of new series of substituted 3,4-dihydrothieno[2,3-d]pyrimidines. The newly synthesized compounds were preliminary tested for their in vitro activity against six bacterial and three fungal strains using the agar diffusion technique. The results revealed that compounds 7 , 8a , 10b , 10d and 11b exhibited half the potency of levofloxacine against the Gram-negative bacterium, Pseudomonas aeruginosa , while compounds 5a , 8b , 10c and 12 displayed half the potency of levofloxacine against Proteus Vulgaris . Whereas, compounds 7 , 10b , 10d and 11b showed half the activity of ampicillin against the Gram-positive bacterium, B. subtilis . Most of the compounds showed high antifungal potency. Compounds 3 , 6 , 7 , 9b , 10a , 11a , 11b , 15 and 16 exhibited double the potency of clotrimazole against A. fumigatus . While compounds 3 , 4 , 5a , 5b , 9b , 10a , 10b , 1 0c , 13 , 15 , 16 and 18 displayed double the activity of clotrimazole against R. oryazae . Molecular docking studies of the active compounds with the active site of the B. anthracis DHPS, showed good scoring for various interactions with the active site of the enzyme compared to the co-crystallized ligand.