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Open AccessArticle

Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase 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
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt
4
Microbiology Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
5
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(20), 3650; https://doi.org/10.3390/molecules24203650
Received: 11 September 2019 / Revised: 3 October 2019 / Accepted: 6 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance)
A series of novel thienopyridines and pyridothienoquinolines (3a,b–14) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles 1a and 1b. All compounds were evaluated for their in vitro antimicrobial activity against six bacterial strains. Compounds 3a,b, 4a, 5b, 6a,b, 7a, 9b, 12b, and 14 showed significant growth inhibition activity against both Gram-positive and Gram-negative bacteria compared with the reference drug. The most active compounds (4a, 7a, 9b, and 12b) against Staphylococcus aureus were also tested for their in vitro inhibitory action on methicillin-resistant Staphylococcus aureus (MRSA). The tested compounds showed promising inhibition activity, with the performance of 12b being equal to gentamicin and that of 7a exceeding it. Moreover, the most promising compounds were also screened for their Escherichia coli DNA gyrase inhibitory activity, compared with novobiocin as a reference DNA gyrase inhibitor. The results revealed that compounds (3a, 3b, 4a, 9b, and 12b) had the highest inhibitory capacity, with IC50 values of 2.26–5.87 µM (that of novobiocin is equal to 4.17 µM). Docking studies were performed to identify the mode of binding of the tested compounds to the active site of E. coli DNA gyrase B. View Full-Text
Keywords: thienopyridines; pyridothienoquinoline; antibacterial; MRSA; DNA gyrase; molecular docking thienopyridines; pyridothienoquinoline; antibacterial; MRSA; DNA gyrase; molecular docking
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MDPI and ACS Style

Mohi El-Deen, E.M.; Abd El-Meguid, E.A.; Hasabelnaby, S.; Karam, E.A.; Nossier, E.S. Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors. Molecules 2019, 24, 3650.

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