Synthesis and the antimicrobial activity of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl)propanoic acids
Keywords:quinolone-4-one, 3-(2-methyl-4-oxo-1, 4-dihydroquinoline-3-yl)propanoic acid, structure-activity relationship, antimicrobial activity
In order to reveal the possible regularities of the structure–activity relationship the derivatives of 3-(2-methyl-4- oxo-1,4-dihydroquinoline-3-yl)propanoic acid having various substituents in α-position of the acidic moiety of propanoic acid such as alkyl, carboxyl, acyl and acetamide substituents have been synthesized. The synthesis of the target compounds has been carried out using 3-dimethylaminomethyl-2-methyl-1,4-dihydroquinoline-4-one as a versatile alkylating reagent. Its interaction with methylene active substances allowed to obtain monoalkyldicarbonyl compounds, which further hydrolysis gave the derivatives of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3yl)propanoic acid. The structures of the compounds obtained have been confirmed by the data of 1H NMR and elemental analysis. The results of the screening performed by the agar diffusion method have shown different levels of the antimicrobial activity. For two compounds – 1,3-diethoxy-2-[(2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)methyl]-1,3-dioxopropan-2-yl-carbamic acid and 3-(2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)propanoic acid a moderate broad-spectrum activity has been found in the screening method. The results of the research have shown the perspectiveness of further search for novel antibacterial agents based on 4-quinolon-3-yl-propanoic acids, therefore, it is necessary to expand the range of the compounds with this scaffold.
Esther T. Kok, Miek C. Jong, Barbara Gravendeel, Willem B. Van Leeuwen, Erik W. Baars. Evidence-Based Complementary and Alternative Medicine, Vol. 2015, Article ID 521584, 6 pages, 2015. doi:10.1155/2015/521584.
Clatworthy A. E., Pierson E., & Hung D. T. Nature Chemical Biology, 2007, Vol. 3(9), pp.541-548. Cited 384 times. doi:10.1038/nchembio.2007.24.
Laxminarayan R. et al. The Lancet Infectious Diseases, 2015, Vol. 13(12), pp.1057-1098. Cited 214 times. doi: 10.1016/S1473-3099(13)70318-9.
Antimicrobial resistance, Fact sheet No.194, Updated April 2015, http://www.who.int/mediacentre/factsheets/fs194/en/.
Andriole Vincent T. Clinical Infectious Diseases, 2005, Vol. 41, pp.113-119. Cited 102 times. doi: 10.1086/428051.
King D. E., Malone R., Lilley S. H. Am Fam Physician, 2000, Vol. 61(9), pp.2741-2748. Cited 128 times.
Ball P. J. Antimicrob. Chemother. 2000, Vol. 46, suppl 3, pp.17-24. doi: 10.1093/oxfordjournals.jac.a020889.
Oldenburg C., Lalitha P., Srinivasan M. etc. Ophthalmic epidemiology, 2013, Vol. 05, pp.20-23. Cited 2 times. doi: 10.3109/09286586.2013.790978.
Morais Cabral J. H., Jackson A. P., Smith C. V., Shikotra N., Maxwell A., Liddington R. C. Nature, 1997, Vol. 388(6645), pp.903-906. Cited 316 times.
Maxwell A. Biochemical Society Transactions, 1999, Vol. 27(2), pp.48-53. Cited 117 times.
Domagala J. M. J. Antimicrob. Chemother, 1994, Vol. 33 (4), pp.685-706. Cited 608 times. doi: 10.1093/jac/33.4.685.
Wohlkonig A., Chan P. F., Fosberry A. P., Homes P. et al. Nat. Struct. Mol. Biol., 2010, Sep, Vol. 17(9), pp.1152-1153. Cited 80 times. doi: 10.1038/nsmb.1892.
Zubkov V. O., Tsapko T. O., Gritsenko I. S., Rushchak N. I. Zhurnal organichnoi ta farmatsevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2011, Vol. 9, No.4, pp.38-41.
Zubkov V. O., Ruschak N. I., Kamenetska O. L., Gritsenko I. S. Zhurnal organichnoi ta farmatsevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2015, Vol. 13, No.4, pp.32-36.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. Document M100-S22, 2012, Vol. 32, No.3, CLSI, Wayne, PA, January.
American Society for Microbiology, Coyle M. B. Manual of Antimicrobial Susceptibility Testing. American Society for Microbiology: Washington, 2005, p.236.
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