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Article

Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors

1
Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt
2
Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, Cairo 12622, Egypt
3
Microbial Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
4
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt
5
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Taif University, Taif 21974, Saudi Arabia
6
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt
*
Author to whom correspondence should be addressed.
Received: 2 September 2020 / Revised: 30 September 2020 / Accepted: 7 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue Design and Synthesis of Antibacterial Heterocycle-Based Compounds)
The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,ba,b) were synthesized by a series of various reactions, starting with 3-aminothieno[2,3-b]pyridine-2-carboxamides (1a,b). Condensation of compounds 1a,b with cyclohexanone gave 1’H-spiro[cyclohexane-1,2’-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin]-4’(3’H)-ones (2a,b), which in turn were utilized to afford the target 4-substituted derivatives (3a,b8a,b). In vitro antibacterial activity evaluations of all the new compounds (2a,b8a,b) were performed against six strains of Gram-negative and Gram-positive bacteria. The target compounds showed significant antibacterial activity, especially against Gram-negative strains. Moreover, the compounds (2a,b; 3a,b; 4a,b; and 5a,b) that exhibited potent activity against Escherichia coli were selected to screen their inhibitory activity against Escherichia coli topoisomerase II (DNA gyrase and topoisomerase IV) enzymes. Compounds 4a and 4b showed potent dual inhibition of the two enzymes with IC50 values of 3.44 µΜ and 5.77 µΜ against DNA gyrase and 14.46 µΜ and 14.89 µΜ against topoisomerase IV, respectively. In addition, docking studies were carried out to give insight into the binding mode of the tested compounds within the E. coli DNA gyrase B active site compared with novobiocin. View Full-Text
Keywords: pyridothienopyrimidines; antibacterial activity; enzyme inhibition; DNA gyrase; topoisomerase IV; molecular docking pyridothienopyrimidines; antibacterial activity; enzyme inhibition; DNA gyrase; topoisomerase IV; molecular docking
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MDPI and ACS Style

Mohi El-Deen, E.M.; Abd El-Meguid, E.A.; Karam, E.A.; Nossier, E.S.; Ahmed, M.F. Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors. Antibiotics 2020, 9, 695. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100695

AMA Style

Mohi El-Deen EM, Abd El-Meguid EA, Karam EA, Nossier ES, Ahmed MF. Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors. Antibiotics. 2020; 9(10):695. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100695

Chicago/Turabian Style

Mohi El-Deen, Eman M., Eman A. Abd El-Meguid, Eman A. Karam, Eman S. Nossier, and Marwa F. Ahmed 2020. "Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors" Antibiotics 9, no. 10: 695. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100695

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