Discovery of novel bis-oxazolidinone compounds as potential potent and selective antitubercular agents |
| |
| Institution: | 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China;2. Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, PR China;1. Instituto de Ciencia de Materiales de Madrid, CSIC, 28049 Madrid, Spain;2. Department of Physics, Imperial College London, London SW7 2AZ, United Kingdom;3. ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot OX11 0QX, United Kingdom;4. Institut Laue-Langevin, 39042 Grenoble Cedex, France;5. Universidad Politécnica de Cartagena, Plaza del Hospital 1, 30202 Cartagena, Spain;6. Instituto de Nanociencia, Nanotecnología y Materiales Moleculares (INAMOL), Universidad de Castilla-La Mancha, 45071 Toledo, Spain;1. Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, United States;2. Department of Physics and Astronomy, University of Delaware, Newark, DE 19716, United States;1. Univ. Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, F-59000, Lille, France;2. Institut Pasteur de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, U1019-UMR8204-CIIL-Centre d''Infection et d''Immunité de Lille, F-59000, Lille, France;3. Unité Microbiologie, Bioorganique et Macromoléculaire (CP206/04), département R3D, Faculté de Pharmacie, Université Libre de Bruxelles, B-1050, Brussels, Belgium;4. Bioversys AG, Hochbergerstrasse 60C, 4057, Basel, Switzerland;5. Structural Biology Brussels, Vlaams Instituut voor Biotechnology (VIB), B-1050, Brussels, Belgium;1. State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China;2. Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Xinyi Road 15, Guangxi 541001, PR China |
| |
| Abstract: | A variety of new mono-oxazolidinone molecules by modifying the C-ring of Linezolid, a marketed antibiotic for MRSA, were synthesized and tested for their in vitro antibacterial activities against several Staphylococcus aureus, Mycobacterium smegmatis and two Gram-negative bacteria strains (Escherichia coli and Pseudomonas aeruginosa). Among them, compounds 4–7 displayed moderate antimicrobial activities. After development of a second oxazolidinone ring in the western part of the mono-oxazolidinone compounds 4–7 by a ring closure reaction with N,N′-carbonyldiimidazole (CDI), we found thus obtained bis-oxazolidinone compounds 22–25 possess excellently inhibitory activities against H37Rv but poor or no effects on other test bacteria. Among them, bis-oxazolidinone compound 22 and 24 are the most potent two compounds with a same MIC value of 0.125 μg/mL against H37Rv virulent strain. Compound 22 also exhibited extremely low cytotoxicity on monkey kidney Vero cells with a selective index (IC50/MIC) over 40,000, which suggested bis-oxazolidinone compound 22 is a promising lead compound for subsequent investigation in search of new antitubercular agents. |
| |
| Keywords: | Tuberculosis Bis-oxazolidinone Antitubercular Selectivity Vero cells |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
