Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents |
| |
| Affiliation: | 1. Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, United States;2. Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, United States;1. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong;2. Department of Microbiology, Faculty of Medicine, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong;1. CIHIDECAR-CONICET-Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2 – Ciudad Universitaria, 1428 Buenos Aires, Argentina;2. Departamento de Ingeniería Química, Instituto Tecnológico de Buenos Aires, Av. Eduardo Madero 399, 1106 Buenos Aires, Argentina;1. Dipartimento di Farmacia e Biotecnologie FaBiT, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy;2. Dipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi 2, Bologna, Italy;3. Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, United States;4. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, United States;1. BioNano Health Guard Research Center (H-GUARD), Daejeon 34141, Republic of Korea;2. Institute of Advanced Composite Materials, Korea Institute of Science and Technology, Jeonbuk 55324, Republic of Korea;3. Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea |
| |
| Abstract: | ![]()
In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin-resistant Staphylococcus aureus (MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most active compound showed a MIC90 value of 3.7 μg/mL against MRSA in a standard microdilution bacterial growth inhibitory assay. This compound protected wax moth worms against MRSA at a dose of 5× MIC using a worm infectious model. This compound also exhibited inhibition of DNA gyrase activity in a DNA gyrase supercoil assay, suggesting the 5,6-dihydroimidazo[2,1-b]thiazoles may target DNA gyrase for the antimicrobial action. |
| |
| Keywords: | Heterocyclic Antimicrobial MRSA DNA gyrase Imidazothiazole |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
