Access to a Library of 1,3-disubstituted-1,2,3-triazenes and Evaluation of their Antimicrobial Properties

Author(s): Insa Seck, Samba F. Ndoye, Lalla A. Ba, Alioune Fall, Abdoulaye Diop, Ismaïla Ciss, Abda Ba, Cheikh Sall, Amadou Diop, Cheikh S. Boye, Generosa Gomez, Yagamare Fall*, Matar Seck*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 9 , 2020


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Graphical Abstract:


Abstract:

Background: Due to the rapid development of microbial resistance, finding new molecules became urgent to counteract this problem.

Objective: The objective of this work is to access 1,2,3-triazene-1,3-disubstituted, a class of molecule with high therapeutic potential.

Methods: Here we describe the access to 17 new triazene including six with an imidazole-1,2,3-triazene moiety and eleven with an alkyl-1,2,3-triazene moiety and their evaluation against five strains: two gram (-): Escherichia coli ATCC 25921 and Pseudomonas aeruginosa ATCC 27253; two gram (+) : Staphylococcus aureus ATCC 38213 and Enterococcus faecalis ATCC 29212; and one fungi: Candida albicans ATCC 24433.

Results: All strains were sensitive and the best MIC, 0.28 µM, is observed for 4c against Escherichia coli ATCC 25921. Compound 9, 3-isopropynyltriazene, appears to be the most interesting since it is active on the five evaluated strains with satisfactory MIC 0.32 µM against Escherichia coli and Pseudomonas aeruginosa and 0.64 µM against Enterococcus faecalis and Pseudomonas aeruginosa.

Conclusion: Comparing the structure activity relationship, electron withdrawing groups appear to increase antimicrobial activity.

Keywords: Strains, Resistance, Triazene, Antimicrobial, Minimal inhibitory concentrations, Bacterial infections.

[1]
Choffnes, E.R.; Relman, D.A.; Mack, A. Antibiotic resistance; The National Academies Press: Washington, DC, 2010.
[2]
Spellberg, B.; Guidos, R.; Gilbert, D.; Bradley, J.; Boucher, H.W.; Scheld, W.M. 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]
[3]
Karchmer, A.W. Nosocomial bloodstream infections: organisms, risk factors, and implications. Clin. Infect. Dis., 2000, 31(Suppl. 4), S139-S143.
[http://dx.doi.org/10.1086/314078] [PMID: 11017863]
[4]
Reed, C.S.; Huigens, R.W., III; Rogers, S.A.; Melander, C. Modulating the development of E. coli biofilms with 2-aminoimidazoles. Bioorg. Med. Chem. Lett., 2010, 20(21), 6310-6312.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.075] [PMID: 20846860]
[5]
Rogers, S.A.; Lindsey, E.A.; Whitehead, D.C.; Mullikin, T.; Melander, C. Synthesis and biological evaluation of 2-aminoimidazole/carbamate hybrid anti-biofilm and anti-microbial agents. Bioorg. Med. Chem. Lett., 2011, 21(4), 1257-1260.
[http://dx.doi.org/10.1016/j.bmcl.2010.12.057] [PMID: 21251823]
[6]
Ceri, H.; Olson, M.E.; Turner, R.J. Needed, new paradigms in antibiotic development. Expert Opin. Pharmacother., 2010, 11(8), 1233-1237.
[http://dx.doi.org/10.1517/14656561003724747] [PMID: 20384540]
[7]
Anderson, G.G.; O’Toole, G.A. Innate and induced resistance mechanisms of bacterial biofilms. Curr. Top. Microbiol. Immunol., 2008, 322, 85-105.
[http://dx.doi.org/10.1007/978-3-540-75418-3_5] [PMID: 18453273]
[8]
Vajs, J.; Proud, C.; Brozovic, A.; Gazvoda, M.; Lloyd, A.; Roper, D.I.; Osmak, M.; Košmrlj, J.; Dowson, C.G. Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis. Eur. J. Med. Chem., 2017, 127, 223-234.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.060] [PMID: 28063354]
[9]
Heischkeil, R. [Effectiveness of trypanocides berenil and pentamidine in rodent malaria (Plasmodium vinckei)]. Z. Tropenmed. Parasitol., 1971, 22(3), 243-249.
[PMID: 5167439]
[10]
Duch, D.S.; Bacchi, C.J.; Edelstein, M.P.; Nichol, C.A. Inhibitors of histamine metabolism in vitro and in vivo. Correlations with antitrypanosomal activity. Biochem. Pharmacol., 1984, 33(9), 1547-1553.
[http://dx.doi.org/10.1016/0006-2952(84)90426-X] [PMID: 6428421]
[11]
Nishiwaki, K.; Okamoto, A.; Matsuo, K.; Kawaguchi, Y.; Hayase, Y.; Ohba, K. Antimalarial activity of 1-aryl-3,3-dialkyltriazenes. Bioorg. Med. Chem., 2007, 15(8), 2856-2859.
[http://dx.doi.org/10.1016/j.bmc.2007.02.027] [PMID: 17329108]
[12]
Bauer, A.W.; Kirby, W.M.; Sherris, J.C.; Turck, M. Antibiotic susceptibility testing by a standardized single disk method. American J. Clin. Patho., 1966, 45(4_ts), 493-496.
[http://dx.doi.org/10.1093/ajcp/45.4_ts.493]
[13]
Kumar, G.S.; Jayaveera, K.N.; Ashok Kumar, C.K.; Umachigi Sanjay, P.; Vrushabendra Swamy, B.M.; Kishore Kumar, D.V. Antimicrobial effects of Indian medicinal plants against acne-inducing bacteria. Trop. J. Pharm. Res., 2007, 6(2), 717-723.
[http://dx.doi.org/10.4314/tjpr.v6i2.14651]
[14]
O’Neill, A.J.; Miller, K.; Oliva, B.; Chopra, I. Comparison of assays for detection of agents causing membrane damage in Staphylococcus aureus. J. Antimicrob. Chemother., 2004, 54(6), 1127-1129.
[http://dx.doi.org/10.1093/jac/dkh476] [PMID: 15531595]
[15]
Cappoen, D.; Vajs, J.; Uythethofken, C.; Virag, A.; Mathys, V.; Kočevar, M.; Verschaeve, L.; Gazvoda, M.; Polanc, S.; Huygen, K.; Košmrlj, J. Anti-mycobacterial activity of 1,3-diaryltriazenes. Eur. J. Med. Chem., 2014, 77, 193-203.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.065] [PMID: 24631899]


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Article Details

VOLUME: 20
ISSUE: 9
Year: 2020
Page: [713 - 719]
Pages: 7
DOI: 10.2174/1568026620666200127143005
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