Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine-Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors.

Autor: Mohi El-Deen EM; Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622, Egypt. e.mohi.2010@live.com., Abd El-Meguid EA; Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, Cairo 12622, Egypt. emannrc@yahoo.com., Hasabelnaby S; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt. sherifajanaa@yahoo.com., Karam EA; Microbiology Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. eman_karam4@yahoo.com., Nossier ES; Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt. dr.emannossier@gmail.com.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2019 Oct 10; Vol. 24 (20). Date of Electronic Publication: 2019 Oct 10.
DOI: 10.3390/molecules24203650
Abstrakt: 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 IC 50 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.
Databáze: MEDLINE
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