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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 20; p. 3650
• Main Authors: Mohi El-Deen, Eman M, Abd El-Meguid, Eman A, Hasabelnaby, Sherifa, Karam, Eman A, Nossier, Eman S
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.10.2019; MDPI
• Subjects: Amoxicillin; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial; Antibacterial activity; Antibacterial agents; Antibiotics; Antimicrobial agents; Apoptosis; Bacteria; Banded structure; Ciprofloxacin; Coliforms; Deoxyribonucleic acid; Dihydropyridine; DNA; dna gyrase; DNA Gyrase - chemistry; DNA topoisomerase; Drug resistance; E coli; Escherichia coli - enzymology; Escherichia coli - growth & development; Escherichia coli Proteins - chemistry; Gram-negative bacteria; Gram-positive bacteria; Infrared spectroscopy; Kinases; Methicillin-Resistant Staphylococcus aureus - enzymology; Methicillin-Resistant Staphylococcus aureus - growth & development; Microorganisms; Minimum inhibitory concentration; molecular docking; Molecular Docking Simulation; mrsa; Ofloxacin; Organic compounds; Pseudomonas aeruginosa; Pyridines; pyridothienoquinoline; Quinoline; Quinolines; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Refluxing; Salmonella; Sodium; Spectra; Staphylococcus aureus; Staphylococcus infections; System effectiveness; thienopyridines; Thienopyridines - chemical synthesis; Thienopyridines - chemistry; Thienopyridines - pharmacology; Topoisomerase II Inhibitors - chemical synthesis; Topoisomerase II Inhibitors - chemistry; Topoisomerase II Inhibitors - pharmacology; antibacterial; molecular docking; DNA gyrase; thienopyridines; pyridothienoquinoline; MRSA
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24203650

A series of novel thienopyridines and pyridothienoquinolines ( ) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles and . All compounds were evaluated for their in vitro antimicrobial activity against six bacterial strains. Compounds and showed significant growth inhibition activity against both Gram-positive and Gram-negative bacteria compared with the reference drug. The most active compounds ( and ) against were also tested for their in vitro inhibitory action on methicillin-resistant (MRSA). The tested compounds showed promising inhibition activity, with the performance of being equal to gentamicin and that of exceeding it. Moreover, the most promising compounds were also screened for their DNA gyrase inhibitory activity, compared with novobiocin as a reference DNA gyrase inhibitor. The results revealed that compounds ( and ) had the highest inhibitory capacity, with IC 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 DNA gyrase B.