Generic placeholder image

Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Research Article

Antimicrobial Activity of Highly Fluorinated Thiocarbamates and Dithiocarbamates

Author(s): Amal Thebti, Ines Chniti, Med Abderrahmane Sanhoury*, Ikram Chehidi, Hadda Imene Ouzari and Abdellatif Boudabous

Volume 13, Issue 2, 2019

Page: [120 - 128] Pages: 9

DOI: 10.2174/2212796812666180907153901

Price: $65


Background: The widespread occurrence of resistance to current antibiotics has triggered increasing research efforts to design and develop innovative antibacterial and antifungal agents that could overcome such antimicrobial resistance.

Objective: The aim of this work was the in vitro evaluation of twelve highly fluorinated Nmonosubstituted thiocarbamates and dithiocarbamates and six non-fluorinated analogs against nine bacterial strains and three fungal species.

Methods: The in vitro antimicrobial activity against the tested microrganisms was evaluated using the microdilution broth method.

Results: Escherichia coli ATCC 8739, Salmonella sp., Staphylococcus aureus 6539 and all the three fungi (Aspergillus niger, Aspergillus flavus and Penicillium expansum) exhibited the highest rate of susceptibility, whilst Enterococcus faecuim ATCC 19436 and particularly Escherichia coli DH5α were less susceptible. Thiocarbamate (1i) and dithiocarbamate (2i) showed both the lowest MIC values (3.9 µg/mL) and the widest spectrum of antibacterial activity. Furthermore, the N-ethyl derivatives inhibited more efficiently the growth of bacteria than N-aryl analogs.

Conclusion: The fluorinated compounds showed, in general, a relatively more potent antibacterial activity than non-fluorinated counterparts. The results indicate that these thiocarbamates and dithiocarbamates could be promising candidates as potential antimicrobial agents.

Keywords: Thiocarbamates, dithiocarbamates, fluoroalkyl, antibacterial and antifungal activities, N-aryl analogs, antimicrobial agents.

Graphical Abstract
Charles PG, Grayson ML. The dearth of new antibiotic development: Why we should be worried and what we can do about it. Med J Aust 2004; 181: 549-53.
Levy SB. Antibiotic resistance-the problem intensifies. Adv Drug Deliv Rev 2005; 57: 1446-50.
Normark BH, Normark S. Evolution and spread of antibiotic resistance. J Intern Med 2002; 252: 91-106.
Odonkor ST, Addo KK. Bacteria resistance to antibiotics: Recent trends and challenges. Int J Biol Med Res 2011; 2: 1204-10.
Livermore DM. Fourteen years in resistance. Int J Antimicrob Agents 2012; 39: 283-94.
Gallucci MN, Carezzano ME, Oliva MM, et al. In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: A quantitative structure-activity relationship analysis. J Appl Microbiol 2014; 116: 795-804.
Brickner SJ, Hutchinson DK, Barbachyn MR, et al. Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. J Med Chem 1996; 39: 673-9.
a) Johnson AP, Tysall L, Stockdale MW, et al. Emerging linezolid-resistant Enterococcus faecalis and Enterococcus faeciumisolated from two Austrian patients in the same intensive care unit. Eur J Clin Microbiol Infect Dis 2002; 21: 751-4.; b) Auckland C, Teare L, Cooke F, et al. Linezolid-resistant enterococci: Report of the first isolates in the United Kingdom. J Antimicrob Chemother 2002; 50: 743-6.
Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001; 358: 207-31.; b) Wilson p , Andrews JA, , Charlesworth R, , et al. Linezolid resistance in clinical isolates of Staphylococcus aureus. J Antimicrob Chemother 2003; 51: 186-8.
Krátký M, Volková M, Novotná E, et al. Synthesis and biological activity of new salicylanilide N,N-disubstituted carbamates and thiocarbamates. Bioorg Med Chem 2014; 22: 4073-82.
Ryder NS, Frank I, Dupont MC. Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agentstolnaftate and tolciclate. Antimicrob Agents Chemother 1986; 29: 858-60.
Mukherjee PK, Leidich SD, Isham N, et al. Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother 2003; 47: 82-6.
Krátký M, Vinšová J. Salicylanilide N-monosubstituted carbamates: Synthesis and in vitro antimicrobial activity. Bioorg Med Chem 2016; 24: 1322-30.
Jang S-Y, Ha YH, Ko SW, et al. Synthesis and antibacterial activity of arylpiperazinyloxazolidinones with diversification of the N-substituents. Bioorg Med Chem Lett 2004; 14: 3881-3.
Thayer AM. Rapid screening and optimization of enzymatic activity, along with available, easy-to-use enzymes, are making biocatalysis a handy tool for chiral synthesis. Chem Eng News 2006; 84: 15-25.
Kirk KL. Fluorination in medicinal chemistry: Methods, strategies, and recent developments. Org Process Res Dev 2008; 12: 305-21.
Hagmann WK. The many roles for fluorine in medicinal chemistry. J Med Chem 2008; 51: 4359-69.
Prakash GKS, Chacko S. Novel nucleophilic and electrophilic fluoroalkylation methods. Curr Opin Drug Discov Devel 2008; 11: 793-802.
Furuya T, Kuttruff CA, Ritte T. Carbon–fluorine bond formation. Curr Opin Drug Discov Devel 2008; 11: 803-19.
Wu J, Cao S, Liu N, et al. A general strategy for construction of a difluoromethyl compound library and its application in synthesis of pseudopeptides bearing a terminal difluoromethyl group. Org Biomol Chem 2010; 8: 2386-91.
Meanwell NA. Synopsis of some recent tactical application of bioisosteres in drug design. J Med Chem 2011; 54: 2529-91.
Rewcastle GW, Gamage SA, Flanagan JU, Frederic R, Denny WA. Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J Med Chem 2011; 54: 7105-26.
Chniti I, Sanhoury MAK, Chehidi I. O-perfluoroalkylthiocarbamates: Synthesis and perfluoroalkyl effects on the barrier to N-CS rotation. J Fluor Chem 2013; 156: 101-5.
Chniti I, Sanhoury MAK, Merlet D, Chehidi I. Synthesis and conformational study of new S-polyfluoroalkyldithiocarbamates. J Fluor Chem 2014; 168: 223-9.
Belkacem-Hanfi N, Fhoula I, Semmar N, et al. Lactic acid bacteria against post-harvest moulds and ochratoxin A isolated from stored wheat. Biol Control 2014; 76: 52-9.
Chahad OB, Bour ME, Calo-Mata P, Boudabous A, Barros-Velazquez J. Discovery of novel biopreservation agents with inhibitory effects on growth of food-borne pathogens and their application to seafood products. Res Microbiol 2012; 163: 44-54.
Klibi N, Ben Amor I, Rahmouni M, et al. Diversity of species and antibiotic resistance among fecal enterococci from wild birds in Tunisia. Detection of vanA-containing Enterococcus faecium isolates. Eur J Wildl Res 2015; 61: 319-23.
Tayh G, Ben Sallem R, Ben Yahia H, et al. First report of extended-spectrum β-lactamases among clinical isolates of Escherichia coli in Gaza Strip, Palestine. J Glob Antimicrob Resist 2016; 6: 17-21.
Reference method for broth dilution antifungal susceptibility testing of yeasts, approved standard. 3rd ed. Wayne, PA: Clinical laboratory standards institute (CLSI) 2008.
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A4. Wayne, PA: National committee for clinical laboratory standards 2000.
Zhang L, Jiao B, Yang X, Liu L, Ma S. Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether. J Antibiot 2011; 64: 243-7.
Krátky M, Bosze S, Baranyai Z, et al. Synthesis and in vitro biological evaluation of 2-(phenylcarbamoyl)phenyl 4-substituted benzoates. Bioorg Med Chem 2015; 23: 868-75.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy