Synthesis and molecular docking study of some 3,4-dihydrothieno[2,3-d]pyrimidine derivatives as potential antimicrobial agents.

Autor: Shaaban OG; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt. Electronic address: omaima.shaaban@pua.edu.eg., Issa DAE; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon., El-Tombary AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt., Abd El Wahab SM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Damanhour University, Beheira, Egypt., Abdel Wahab AE; Genetic Engineering and Biotechnology Research Institute (GEBRI), The City for Scientific Research and Technology Application, Borg El-Arab, Alexandria, Egypt., Abdelwahab IA; Department of Microbiology and Immunology, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Jul; Vol. 88, pp. 102934. Date of Electronic Publication: 2019 Apr 16.
DOI: 10.1016/j.bioorg.2019.102934
Abstrakt: In continuation of our research program aiming at developing new potent antimicrobial agents, new series of substituted 3,4-dihydrothieno[2,3-d]pyrimidines was synthesized. 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, 10c, 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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