Synthesis of alkynylated 1,2,4-oxadiazole/1,2,3-1H-triazole glycoconjugates: Discovering new compounds for use in chemotherapy against lung carcinoma and Mycobacterium tuberculosis

Oliveira, Valentina Nascimento Melo de; Moura, Cybele Flávia do Amaral; Peixoto, Aline dos Santos; Ferreira, Vanessa Pinheiro Gonçalves; Araújo, Héverton Mendes; Pimentel, Lílian Maria Lapa Montenegro; Pessoa, Cláudia; Nicolete, Roberto; Anjos, Janaina Versiani dos; Sharma, Prem Prakash; Rathi, Brijesh; Pena, Lindomar; Rollin, Patrick; Tatibouët, Arnaud; Oliveira, Ronaldo N. de

doi:10.1016/j.ejmech.2021.113472

Cited by 21 publications

(5 citation statements)

References 51 publications

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“…Here using high content imaging on human MTBinfected macrophages, we identified 1,2,4-oxadiazole based compounds, with no effect on MTB growth in liquid culture, but able to inhibit the intracellular mycobacterial growth inside the host in a concentration dependent manner. Interestingly, these compounds have no similarity to other published 1,2,4-oxadiazole derivatives with activity on MTB (38)(39)(40).…”

Section: Discussionmentioning

confidence: 78%

An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning

Maure¹,

Lawarée²,

Fiorentino³

et al. 2023

Preprint

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Anti-tuberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains of Mycobacterium tuberculosis are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high content imaging, we identified novel 1,2,4-oxadiazole-based compounds, that allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, M. tuberculosis became even more sensitive to anti-tuberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

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Section: Discussionmentioning

confidence: 78%

An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning

Maure¹,

Lawarée²,

Fiorentino³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Here, using high-content imaging on human MTB-infected macrophages, we identified 1,2,4-oxadiazole-based compounds, with no effect on MTB growth in liquid culture, but able to inhibit the intracellular mycobacterial growth inside the host in a concentration-dependent manner. Interestingly, these compounds have no similarity to other published 1,2,4-oxadiazole derivatives with activity on MTB [ 43 – 45 ].…”

Section: Discussionmentioning

confidence: 97%

A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection

Maure,

Lawarée,

Fiorentino

et al. 2024

PLoS Biol

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Antituberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multiresistant strains of Mycobacterium tuberculosis (MTB) are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high-content imaging, we identified novel 1,2,4-oxadiazole-based compounds, which allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, MTB became even more sensitive to antituberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

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“…Melo de Oliveira et al [57] synthesized alkynylated 1,2,4oxadiazole/1,2,3-1H-triazole glycol conjugates and evaluated their in vitro antitubercular efficacy against M. tuberculosis (Mtb) H37Ra and H37Rv strains. Derivatives 38 (MIC = 10 mM) and 39 (MIC = 23.9 mM) were the most promising antitubercular agents.…”

Section: Antitubercular Activitymentioning

confidence: 99%

1,2,3-Triazole Containing Hybrids as Potential Pharmacological Agents: A Review

Masood,

Iqbal

2024

ajc

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1,2,3-Triazoles constitute a versatile class of nitrogen containing five-membered heterocycles, exhibiting wide range of pharmacological properties which include antibacterial, antifungal, anticancer, antimalarial, antidiabetic, anti-inflammatory, antihypertensive and antioxidant, among various others. Medicinal chemists have been interested in this aromatic ring as a framework since the inception of click chemistry as considered as the building block of contemporary organic chemistry. Extensive research into this framework’s linker characteristic has led to the synthesis and evaluation of numerous 1,2,3-triazole hybrids bearing a wide range of heterocyclic moieties as potential leads for various biological targets. This molecular hybridization has also added advantage of the improved pharmacological activity overcoming the problem of multiple drug resistance and reduced toxicity. This review summarizes the pharmacological activities of various 1,2,3-triazole containing hybrids and conjugates, covering articles published in past decade (2013 till date) and will be of great assistance to medicinal chemistry researchers in providing a useful direction for the future drug discovery.

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Synthesis of alkynylated 1,2,4-oxadiazole/1,2,3-1H-triazole glycoconjugates: Discovering new compounds for use in chemotherapy against lung carcinoma and Mycobacterium tuberculosis

Cited by 21 publications

References 51 publications

An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning

An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning

A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection

1,2,3-Triazole Containing Hybrids as Potential Pharmacological Agents: A Review

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