Effectiveness of Novel 5‐(5‐amino‐1‐aryl‐1H‐pyrazol‐4‐yl)‐1H‐tetrazole Derivatives Against Promastigotes and Amastigotes of Leishmania amazonensis

Faiões, Viviane dos Santos; Leon, Leonor L.; Canto‐Cavalheiro, Marilene M.; Torres-Santos, Eduardo Caio; Bernardino, Alice M. R.; Vegi, Percilene Fazolin; Santos, Maurício Silva dos

doi:10.1111/cbdd.12235

Cited by 9 publications

(3 citation statements)

References 17 publications

(14 reference statements)

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“…reported the antileishmanial potential of arylpyrazole based tetrazoles. The synthesized arylpyrazole based tetrazoles displayed potent and innovative antileishmanial response [18] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Aziz

Saeed

Jabeen

et al. 2018

Heliyon

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Tetrazoles are conjugated nitrogen-rich heterocycles considered as bio-isosteres of carboxylic acids. Tetrazoles owing to their conjugated structures serve as biologically relevant potent scaffolds. The present research paper reports the successful synthesis and single crystal analysis of three different tetrazole derivatives (2, 4, 6). The synthesized tetrazole derivatives were evaluated for their possible cytotoxicity LD50 (52.89, 49.33, 17.28 μg/ml) and antileishmanial activities IC50 (0.166, 10, 5.0 μg/ml). Moreover, molecular docking studies were performed to determine the possible interaction sites of the tetrazole derivatives (2, 4, 6) with TryR, an enzyme involved in the redox metabolism of the Leishmania parasite. Docking computations demonstrates that the tetrazole derivatives (2, 4, 6) established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. The results suggested that the synthesized tetrazole derivative (2, 4, 6) can be possible hit candidates which can be tested further against amastigote stage of parasite and then in an animal model of leishmaniasis.

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“…reported the antileishmanial potential of arylpyrazole based tetrazoles. The synthesized arylpyrazole based tetrazoles displayed potent and innovative antileishmanial response [18] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Aziz

Saeed

Jabeen

et al. 2018

Heliyon

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“…Of note, several pyrazole-based series of antileishmanial compounds have been reported by research groups in Brazil, but these generally have modest–weak activity against Leishmania species (e.g., L. amazonensis) that cause cutaneous leishmaniasis (CL), not VL. ,,− Consequently, there is an urgent need for additional research into more effective therapeutic options for the treatment of VL. − …”

Section: Introductionmentioning

confidence: 99%

Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

et al. 2015

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Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound 26 shows high levels of in vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof of concept for this series.

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“…Allopurinol, a pyrazolylpyrimidine, has been used as an antileishmanial drug since the 1970s, and it is employed as an alternative to antimonials in specific cases. In previous studies, we planned, synthesized, and evaluated the antileishmanial activities of a series of pyrazolyltetrazole hybrids with halogen substitutions in the phenyl ring (14). In the present study, following a rational drug design approach, we replaced the halogens with an electron-donating substituent (OMe), yielding 5-[5-amino-1-(4=-methoxyphenyl) 1H-pyrazole-4-yl]1H-tetrazole (MSN20), which exhibits improved antileishmanial activity and is orally bioavailable in mice, as described here.…”

mentioning

confidence: 99%

The New Pyrazolyltetrazole Derivative MSN20 Is Effective via Oral Delivery against Cutaneous Leishmaniasis

Faiões

Santos

Bernardino³

et al. 2014

Antimicrob Agents Chemother

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An orally delivered, safe and effective treatment for leishmaniasis is an unmet medical need. Azoles and the pyrazolylpyrimidine allopurinol present leishmanicidal activity, but their clinical efficacies are variable. Here, we describe the activity of the new pyrazolyltetrazole hybrid, 5-[5-amino-1-(4=-methoxyphenyl)1H-pyrazole-4-yl]1H-tetrazole (MSN20). MSN20 showed a 50% inhibitory concentration (IC 50 ) of 22.3 M against amastigotes of Leishmania amazonensis and reduced significantly the parasite load in infected mice, suggesting its utility as a lead compound for the development of an oral treatment for leishmaniasis.

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Effectiveness of Novel 5‐(5‐amino‐1‐aryl‐1H‐pyrazol‐4‐yl)‐1H‐tetrazole Derivatives Against Promastigotes and Amastigotes of Leishmania amazonensis

Cited by 9 publications

References 17 publications

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Synthesis, single crystal analysis, biological and docking evaluation of tetrazole derivatives

Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

The New Pyrazolyltetrazole Derivative MSN20 Is Effective via Oral Delivery against Cutaneous Leishmaniasis

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