Anti-mycobacterial activity of 1,3-diaryltriazenes

Cappoen, Davie; Vajs, Jure; Uythethofken, Cynthia; Virag, Andrej; Mathys, Vanessa; Kočevar, Marijan; Verschaeve, Luc; Gazvoda, Martin; Polanc, Slovenko; Huygen, Kris; Košmrlj, Janez

doi:10.1016/j.ejmech.2014.02.065

Cited by 26 publications

(21 citation statements)

References 26 publications

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“…In view of the biological activities of the triazenes with mentioned scaffold [31,47], considering the information obtained from ADME properties of the synthesized ligand would be valuable. In this study, the pharmacokinetic features of the five synthesized triazenes were predicted through projection on some predefined models provided by volSurf.…”

Section: Pharmacokinetic Studiesmentioning

confidence: 99%

“…Recently, the efforts in this field resulted in achievement to the reliable models that can be used in prediction the pharmacokinetic behaviour of a compound [29,30]. High similarity of the synthesized ligands to some drug candidates [31] encourage us to study their pharmacokinetics. In this work, in order to investigate the pharmacokinetic behaviour of the prepared ligand, in silico ADME studies were performed by projection their 3D structures on the pre-calculated models developed in VolSurf program.…”

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confidence: 99%

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Synthesis, Crystal Structure, Solution Study and In Silico ADME Profiling of Various Asymmetric Functionalized Triazenes

Gharamaleki

Goodarzi

Bolouhari

et al. 2015

J Inorg Organomet Polym

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Syntheses of some ligands based on asymmetric triazenes consisting 1-(2-methoxycarbonylphenyl)-3-(2-methylphenyl)triazene (1), 1-(2-methoxycarbonylphenyl)-3-(3-methylphenyl)triazene (2), 1-(2-methoxycarbonylphenyl)-3-(4-methylphenyl)triazene (3), 1-(2-methoxycarbonylphenyl)-3-(3,5-dichlorophenyl)triazene (4), 1-(4-chlorophenyl)-3-(4-methylphenyl)-triazene (5) and their related Hg II complexes were reported. The characterizations were performed by FT-IR, 1 H NMR and 13 C NMR spectroscopies. In (3) and (4), both triazenes possess trans-conformation around the (-N=N-) bond and monomeric moieties are linked to pairs and wave-like chains through C-HÁÁÁO and C-HÁÁÁN hydrogen bonds which are further assembled by stacking through secondary pÁÁÁp interactions [3.829(1) and 3.736(1) Å ]. The reaction of (1) and Hg(NO 3 ) 2 in methanol produces the corresponding Hg II complex (6) where each triazenide binds to the Hg II atom through two nitrogen atoms of triazenide and one oxygen atom of pendant methoxycarbonyl group forming distorted MN 4 O 2 octahedral around the Hg II atom. The stoichiometry and formation of complex (6) and (8) in methanol solution were investigated by UV-Vis titration. Moreover, Reaction of substituted 1,3-diaryltriazenes (2) and (5) with Hg II salts afford a family of orange complexes (7) and (8), respectively. Finally, the chemical structures of the investigated ligands were correlated to their pharmacokinetic behaviour using five pre-calculated models implemented in VolSurf program. Graphical Abstract Polyhedron around HgII atom coordinated by two triazenide ligands in an octahedron fashion.

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Section: Pharmacokinetic Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis, Crystal Structure, Solution Study and In Silico ADME Profiling of Various Asymmetric Functionalized Triazenes

Gharamaleki

Goodarzi

Bolouhari

et al. 2015

J Inorg Organomet Polym

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“…[1] Consequently, TB is on the list of the leading ten causes of death worldwide and is now the most lethal disease caused by a single infectious agent, surpassing even the HIV/AIDS pandemic. [4] Berenil ® or diminazene aceturate ( Figure 1a) has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. Because the recommended TB treatment is very demanding on the patient, non-compliance has contributed to the emergence of strains of drug-resistant M. tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro investigation of halogenated 1,3‐bis(4‐nitrophenyl)triazenide salts as antitubercular compounds

et al. 2017

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The diverse pharmacological properties of the diaryltriazenes have sparked the interest to investigate their potential to be repurposed as antitubercular drug candidates. In an attempt to improve the antitubercular activity of a previously constructed diaryltriazene library, eight new halogenated nitroaromatic triazenides were synthesized and underwent biological evaluation. The potency of the series was confirmed against the Mycobacterium tuberculosis lab strain H37Ra, and for the most potent derivative, we observed a minimal inhibitory concentration of 0.85 μm. The potency of the triazenide derivatives against M. tuberculosis H37Ra was found to be highly dependent on the nature of the halogenated phenyl substituent and less dependent on cationic species used for the preparation of the salts. Although the inhibitory concentration against J774A.1 macrophages was observed at 3.08 μm, the cellular toxicity was not mediated by the generation of nitroxide intermediate as confirmed by electron paramagnetic resonance spectroscopy, whereas no in vitro mutagenicity could be observed for the new halogenated nitroaromatic triazenides when a trifluoromethyl substituent was present on both the aryl moieties.

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“…This selection was stimulated by our recent observation on strong in vitro activity of electron-deficient triazenes against M. tuberculosis. 6 To effectively participate in modulating the electron density, ortho-and/or para-substitution pattern relative to the triazene group was selected predominantly. #R6#Some 1,3-diaryltriazenes were modified by N-acylation.…”

Section: Chemistrymentioning

confidence: 99%

“…5 Based on our recent research 6 we were prompted to further explore the antimicrobial activity of 1,3-diaryltriazenes. Triazenes possess a number of biological properties, including antifungal, 7 anorexic, 8 and anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis

Vajs

Proud

Brozović

et al. 2017

European Journal of Medicinal Chemistry

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Antibiotic resistance poses a critical threat to global health care. Alkyl-and aryltriazene compounds have found utility as DNA-modifying agents and have been previously 2 assessed as potential anti-cancer therapeutics. However, their potential utility as antimicrobials has only recently been appreciated. Therefore, to further investigate the efficacy of these compounds as antibiotics, we synthesized a series of forty six diaryltriazene derivatives and evaluated their antimicrobial properties. Initial experiments showed activity of some diaryltriazene compounds against both methicillin-resistant strains of Staphylococus aureus (MRSA) and against Mycobacterium smegmatis with MICs of less than 0.02 and 1 μg/mL. Those diaryltriazene compounds with potent anti-staphylococcal and anti-mycobacterial activity were inactive as growth inhibitors of mammalian cell lines and yeast. Furthermore, we demonstrated that one of the most active anti-MRSA diaryltriazene derivatives was subject to very low frequencies of resistance at < 10 -9 . Whole genome sequencing of resistant isolates identified mutations in the enzyme that lysylates phospholipids. This could result in the modification of phospholipid metabolism and consequently the characteristics of the staphylococcal cell membrane, ultimately modifying the sensitivity of these pathogens to triazene challenge. Our work has therefore extended the potential range of triazenes, which could yield novel antimicrobials with low levels of resistance.

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Anti-mycobacterial activity of 1,3-diaryltriazenes

Cited by 26 publications

References 26 publications

Synthesis, Crystal Structure, Solution Study and In Silico ADME Profiling of Various Asymmetric Functionalized Triazenes

Synthesis, Crystal Structure, Solution Study and In Silico ADME Profiling of Various Asymmetric Functionalized Triazenes

Synthesis and in vitro investigation of halogenated 1,3‐bis(4‐nitrophenyl)triazenide salts as antitubercular compounds

Diaryltriazenes as antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA) and Mycobacterium smegmatis

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