Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Research Article

Synthesis and Biological Evaluation of Novel Oxazolidinone Derivatives Containing Dithiocarbamate Moiety as Antibacterial Agents

Author(s): Xiudong Ding, Zhanfeng Gao, Siyu Liu, Sicong Xu, Zhiwei Li, Jia Jiang, Ruixi Fan, Tong Chen, Yanfang Zhao, Hengzhi Lu* and Yunlei Hou*

Volume 21, Issue 5, 2024

Published on: 16 February, 2023

Page: [928 - 937] Pages: 10

DOI: 10.2174/1570180820666230118124058

Price: $65

Abstract

Background: In this article, a series of novel oxazolidinone derivatives containing dithiocarbamate moieties have been designed and synthesized.

Materials and Methods: Their antibacterial activities were measured against Staphylococcus aureus, vancomycin-resistant Enterococcus faecium (VREF), linezolid-resistant Enterococcus faecalis (LREF) and Streptococcus agalactiae (GBS) by minimal inhibitory concentration (MIC) assays.

Results: Dithiocarbamates were found conducive to the maintenance of antibacterial activity. Most of them exhibited potent activity against Gram-positive pathogens comparable to linezolid. The most promising compound A8 showed remarkable antibacterial activity against S.aureus, VREF, LREF, and GBS pathogens with MIC values between 0.25 and 1 μg/mL, which might be a promising drug candidate for further investigation.

Conclusion: A series of novel oxazolidinone derivatives containing dithiocarbamate moieties might be promising drug candidates for further investigation.

Keywords: Oxazolidinone derivatives, dithiocarbamate moiety, antibacterial activities, Gram-positive bacteria, drug design, drug synthesis.

« Previous Next »
Graphical Abstract

[1]
Song, Y.; Bai, J.; Zhang, R.; He, H.; Li, C.; Wang, J.; Li, S.; Peng, Y.; Ning, B.; Wang, M.; Gao, Z. Michael-addition-mediated photonic crystals allow pretreatment-free and label-free sensoring of ciprofloxacin in fish farming water. Anal. Chem., 2018, 90(2), 1388-1394.
[http://dx.doi.org/10.1021/acs.analchem.7b04655] [PMID: 29243476]
[2]
Natan, M.; Gutman, O.; Lavi, R.; Margel, S.; Banin, E. Killing mechanism of stable N-halamine cross-linked polymethacrylamide nanoparticles that selectively target bacteria. ACS Nano, 2015, 9(2), 1175-1188.
[http://dx.doi.org/10.1021/nn507168x] [PMID: 25602279]
[3]
Sharaha, U.; Rodriguez-Diaz, E.; Riesenberg, K.; Bigio, I.J.; Huleihel, M.; Salman, A. Using infrared spectroscopy and multivariate analysis to detect antibiotics’ resistant Escherichia coli bacteria. Anal. Chem., 2017, 89(17), 8782-8790.
[http://dx.doi.org/10.1021/acs.analchem.7b01025] [PMID: 28731324]
[4]
Spellberg, B.; Guidos, R.; Gilbert, D.; Bradley, J.; Boucher, H.W.; Scheld, W.M.; Bartlett, J.G.; Edwards, J., Jr The epidemic of antibiotic-resistant infections: a call to action for the medical community from the infectious diseases Society of America. Clin. Infect. Dis., 2008, 46(2), 155-164.
[http://dx.doi.org/10.1086/524891] [PMID: 18171244]
[5]
Takrouri, K.; Cooper, H.D.; Spaulding, A.; Zucchi, P.; Koleva, B.; Cleary, D.C.; Tear, W.; Beuning, P.J.; Hirsch, E.B.; Aggen, J.B. Progress against Escherichia coli with the oxazolidinone class of antibacterials: Test case for a general approach to improving whole-cell Gram-negative activity. ACS Infect. Dis., 2016, 2(6), 405-426.
[http://dx.doi.org/10.1021/acsinfecdis.6b00003] [PMID: 27627629]
[6]
Zhao, Q.; Xin, L.; Liu, Y.; Liang, C.; Li, J.; Jian, Y.; Li, H.; Shi, Z.; Liu, H.; Cao, W. Current landscape and future perspective of oxazolidinone scaffolds containing antibacterial drugs. J. Med. Chem., 2021, 64(15), 10557-10580.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00480] [PMID: 34260235]
[7]
Caroline, P.M.; Linezolid, J.B. A review of its use in the management of serious gram-positive infections. Drugs, 2003, 63(19), 2126-2126.
[8]
Brickner, S.J.; Barbachyn, M.R.; Hutchinson, D.K.; Manninen, P.R. Linezolid (ZYVOX), the first member of a completely new class of antibacterial agents for treatment of serious gram-positive infections. J. Med. Chem., 2008, 51(7), 1981-1990.
[http://dx.doi.org/10.1021/jm800038g] [PMID: 18338841]
[9]
Tsiodras, S.; Gold, H.S.; Sakoulas, G.; Eliopoulos, G.M.; Wennersten, C.; Venkataraman, L.; Moellering, R.C., Jr; Ferraro, M.J. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet, 2001, 358(9277), 207-208.
[http://dx.doi.org/10.1016/S0140-6736(01)05410-1] [PMID: 11476839]
[10]
Auckland, C.; Teare, L.; Cooke, F.; Kaufmann, M.E.; Warner, M.; Jones, G.; Bamford, K.; Ayles, H.; Johnson, A.P. Linezolid-resistant enterococci: Report of the first isolates in the United Kingdom. J. Antimicrob. Chemother., 2002, 50(5), 743-746.
[http://dx.doi.org/10.1093/jac/dkf246] [PMID: 12407134]
[11]
Morales, G.; Picazo, J.J.; Baos, E.; Candel, F.J.; Arribi, A.; Peláez, B.; Andrade, R.; de la Torre, M.Á.; Fereres, J.; Sánchez-García, M. Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin. Infect. Dis., 2010, 50(6), 821-825.
[http://dx.doi.org/10.1086/650574] [PMID: 20144045]
[12]
Ippolito, J.A.; Kanyo, Z.F.; Wang, D.; Franceschi, F.J.; Moore, P.B.; Steitz, T.A.; Duffy, E.M. Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit. J. Med. Chem., 2008, 51(12), 3353-3356.
[http://dx.doi.org/10.1021/jm800379d] [PMID: 18494460]
[13]
Hou, Y.; Dong, Y.; Ye, T.; Jiang, J.; Ding, L.; Qin, M.; Ding, X.; Zhao, Y. Synthesis and antibacterial evaluation of novel oxazolidinone derivatives containing a piperidinyl moiety. Bioorg. Med. Chem. Lett., 2019, 29(23), 126746.
[http://dx.doi.org/10.1016/j.bmcl.2019.126746] [PMID: 31676225]
[14]
Jiang, J.; Hou, Y.; Duan, M.; Wang, B.; Wu, Y.; Ding, X.; Zhao, Y. Design, synthesis and antibacterial evaluation of novel oxazolidinone derivatives nitrogen-containing fused heterocyclic moiety. Bioorg. Med. Chem. Lett., 2021, 32, 127660.
[http://dx.doi.org/10.1016/j.bmcl.2020.127660] [PMID: 33144245]
[15]
Wu, Y.; Ding, X.; Yang, Y.; Li, Y.; Qi, Y.; Hu, F.; Qin, M.; Liu, Y.; Sun, L.; Zhao, Y. Optimization of biaryloxazolidinone as promising antibacterial agents against antibiotic-susceptible and antibiotic-resistant gram-positive bacteria. Eur. J. Med. Chem., 2020, 185, 111781.
[http://dx.doi.org/10.1016/j.ejmech.2019.111781] [PMID: 31654879]
[16]
Shinde, S.D.; Sakla, A.P.; Shankaraiah, N. An insight into medicinal attributes of dithiocarbamates: Bird’s eye view. Bioorg. Chem., 2020, 105, 104346.
[http://dx.doi.org/10.1016/j.bioorg.2020.104346] [PMID: 33074122]
[17]
Imamura, H.; Ohtake, N.; Jona, H.; Shimizu, A.; Moriya, M.; Sato, H.; Sugimoto, Y.; Ikeura, C.; Kiyonaga, H.; Nakano, M.; Nagano, R.; Abe, S.; Yamada, K.; Hashizume, T.; Morishima, H. Dicationic dithiocarbamate carbapenems with anti-MRSA activity. Bioorg. Med. Chem., 2001, 9(6), 1571-1578.
[http://dx.doi.org/10.1016/S0968-0896(01)00044-X] [PMID: 11408176]
[18]
Ren, J.L.; Zhang, E.; Ye, X.W.; Wang, M.M.; Yu, B.; Wang, W.H.; Guo, Y.Z.; Liu, H.M. Design, synthesis and antibacterial evaluation of novel AHL analogues. Bioorg. Med. Chem. Lett., 2013, 23(14), 4154-4156.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.035] [PMID: 23735742]
[19]
Ayman, M.; El-Messery, S.M.; Habib, E.E.; Al-Rashood, S.T.; Almehizia, A.A.; Alkahtani, H.M.; Hassan, G.S. Targeting microbial resistance: Synthesis, antibacterial evaluation, DNA binding and modeling study of new chalcone-based dithiocarbamate derivatives. Bioorg. Chem., 2019, 85, 282-292.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.001] [PMID: 30641322]
[20]
Wang, M.M.; Chu, W.C.; Yang, Y.; Yang, Q.Q.; Qin, S.S.; Zhang, E. Dithiocarbamates: Efficient metallo-β-lactamase inhibitors with good antibacterial activity when combined with meropenem. Bioorg. Med. Chem. Lett., 2018, 28(21), 3436-3440.
[http://dx.doi.org/10.1016/j.bmcl.2018.09.028] [PMID: 30262427]
[21]
Humphries, R.; Bobenchik, A.M.; Hindler, J.A. Overview of changes to the clinical and laboratory standards institute performance standards for antimicrobial susceptibility testing, M100, 31st Edition. J Clin Microbiol., 2021, 18, e0021321.

Rights & Permissions Print Cite
Article Metrics
20
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy