Novel Benzo[1,2-c]1,2,5-Oxadiazole N-Oxide Derivatives as Antichagasic Agents: Chemical and Biological Studies

Olea‐Azar, Claudio; Rigol, Carolina; Mendizábal, Fernando; Cerecetto, Hugo; Maio, Rossanna Di; González, Mercedes; Porcal, Williams; Morello, Antonio; Repetto, Yolanda; Maya, Juan Diego

doi:10.2174/1570180054038341

Cited by 34 publications

(54 citation statements)

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“…ROS can cause direct cellular damage by reacting with various biological macromolecules, or indirect cellular damage by the generation of the highly reactive hydroxyl radical via Haber-Weis and Fenton reactions [2,3].…”

Section: Introductionmentioning

confidence: 99%

Cyclic Voltammetric Study of Some Anti‐Chagas‐Active 1,4‐Dioxidoquinoxalin‐2‐yl Ketone Derivatives

Pérez‐Silanes¹,

Devarapally²,

Torres³

et al. 2013

Helvetica Chimica Acta

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The electrochemical properties of 24 quinoxaline 1,4-di-N-oxide-2-ketone derivatives with varying degrees of anti-chagas activity were investigated in the aprotic solvent dimethylformamide (DMF) using cyclic voltammetry and first derivative cyclic voltammetry. For this group of compounds, the first reduction in DMF was either reversible or quasireversible and consistent with reduction of the N-oxide functionality to form the radical anion. The second reduction process for these compounds was found to be irreversible under the conditions used. The reduction potentials correlated well with molecular structure. Substitution in the 3-, 6-, and 7-positions of the quinoxaline ring by electron-withdrawing substituents directly affects the ease of reduction and improves the biological activities of these compounds, whereas substitution by electrondonating groups has the opposite effect. The results of this study when combined with previous work into their mechanism of action against chagas disease suggest that charge transfer might play a role in the mechanism of action for these compounds.

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Section: Introductionmentioning

confidence: 99%

Cyclic Voltammetric Study of Some Anti‐Chagas‐Active 1,4‐Dioxidoquinoxalin‐2‐yl Ketone Derivatives

Pérez‐Silanes¹,

Devarapally²,

Torres³

et al. 2013

Helvetica Chimica Acta

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“…where n is the number of electrons transferred, F is Faraday's constant, A is the electrode area (cm )), the number of electrons transferred can be calculated through a simple rearrangement as shown in Eqn (2).…”

Section: Resultsmentioning

confidence: 99%

“…3, a T of 295 K, an electrode area of 0.2190 cm 2 , a bulk concentration of 3 × 10 À6 mol/cm 3 and an estimated diffusion coefficient of 2 × 10 À5 cm 2 /s [8] resulted in a calculated one-electron transfer (n = 1.01). This was further supported via potential step chronoamperometry by stepping the potential from 0 V to À3 V and using the well-known Cottrell equation (n = 0.77).…”

Section: Resultsmentioning

confidence: 99%

“…Details of the electrode growing conditions have been reported previously. [14,15] The diamond working electrode was pressed against the bottom of the glass cell and a Chemraz® O-ring (Ace Glass, Inc.) was used to contain the solution and define the exposed electrode area, 0.22 cm 2 . A non-aqueous Ag/AgCl reference electrode (0.01 M AgNO 3 + 0.1 M tetrabutylammonium perchlorate in acetonitrile; CH Instruments) was positioned in close proximity to the working electrode using a cracked-glass capillary filled with electrolyte solution.…”

Section: Methodsmentioning

confidence: 99%

“…The reduction of benzofuroxans has been proposed to proceed via a two-step reduction mechanism, first forming a radical species and subsequently reducing to result in either ring opening of the furoxan or deoxygenation of the ring. [2] Isoxazoles and related compounds have also been shown to undergo electrochemical ring opening. [5] In a similar manner, oximes have been shown to reduce by way of a facile N-O bond cleavage.…”

Section: Introductionmentioning

confidence: 99%

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Electrochemical reduction of 3‐phenyl‐1,2‐benzisoxazole 2‐oxide on boron‐doped diamond

Kociolek

Bennett

Casbohm

2014

J of Physical Organic Chem

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aThe bioreduction of N-oxide compounds is the basis for the mode of action of a number of biologically active molecules. These compounds are thought to act by forming a reactive oxygen species through an intracellular reduction and subsequent redox cycling process within the organism. With these results in mind, the preliminary investigation into the electrochemical reduction of the benzisoxazole 2-oxide ring system was undertaken, with the thought that this class of compounds would reduce in a similar fashion to other N-oxide heterocycles. The electrochemical reduction of 3-phenyl-1,2-benzisoxazole 2-oxide on boron-doped diamond was studied using cyclic and square wave voltammetry as well as controlled potential electrolysis and HPLC for qualitative identification of the reaction products. It was found that the reduction proceeded with an initial quasi-reversible one-electron reduction followed by the very fast cleavage of either the endocyclic or exocyclic N-O bond. Subsequent electron transfer and protonation resulted in an overall two-electron reduction and formation of the 2-hydroxyaryl oxime and benzisoxazole. These results are analogous to those observed in the electrochemical reduction of other heterocyclic N-oxides albeit the reduction of the benzisoxazole N-oxides takes place at a more negative potential. However, these encouraging results warrant further investigation into the reduction potential of substituted benzisoxazole N-oxides as well as to elucidate and characterize the nature of the intermediate species involved.

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Benzofuroxan Derivatives as Potent Agents against Multidrug‐Resistant Mycobacterium tuberculosis

et al. 2021

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Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5] oxadiazole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC 90 values below 0.28 μM against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis.

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Novel Benzo[1,2-c]1,2,5-Oxadiazole N-Oxide Derivatives as Antichagasic Agents: Chemical and Biological Studies

Cited by 34 publications

References 0 publications

Cyclic Voltammetric Study of Some Anti‐Chagas‐Active 1,4‐Dioxidoquinoxalin‐2‐yl Ketone Derivatives

Cyclic Voltammetric Study of Some Anti‐Chagas‐Active 1,4‐Dioxidoquinoxalin‐2‐yl Ketone Derivatives

Electrochemical reduction of 3‐phenyl‐1,2‐benzisoxazole 2‐oxide on boron‐doped diamond

Benzofuroxan Derivatives as Potent Agents against Multidrug‐Resistant Mycobacterium tuberculosis

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