An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis

Duarte, Mariana C.; Lage, Letícia Martins dos Reis; Lage, Daniela P.; Mesquita, Juliana Tonini; Salles, Beatriz C.S.; Lavorato, Stefânia Neiva; Menezes‐Souza, Daniel; Roatt, Bruno Mendes; Alves, Ricardo José; Tavares, Carlos Alberto Pereira; Tempone, André G.; Coelho, Eduardo Antônio Ferraz

doi:10.1016/j.vetpar.2016.01.002

Cited by 38 publications

(18 citation statements)

References 54 publications

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“…The observation that the quinoline alkaloid camptothecin was a potential upstream regulator was also of interest, especially given the progress of the orally active 8‐aminoquinoline sitamaquine (formerly WR‐6026) through preclinical and phase I/II clinical trials against VL in India, Brazil and Kenya (reviewed Ref. ), as well as a similar resurgence of interest in testing known and novel quinoline derivatives . Of interest also in relation to response to drug therapy was the observation of enrichment for a gene set associated with response to arsenic, supporting recent research suggesting that arsenic contamination in drinking water in areas endemic for VL may have led to increased resistance to antimonial compounds like SSB …”

Section: Discussionmentioning

confidence: 84%

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Salih

Fakiola

Lyons

et al. 2017

Parasite Immunology

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Summary Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with sodium stibogluconate (SSG) leads to post‐kala‐azar dermal leishmaniasis (PKDL) in 58% of patients. Here, Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre‐ and post‐treatment with SSG. Using the Bioconductor package limma, 438 genes from 28 869 post‐quality‐control probe sets were differentially expressed (Pnominal≤.02) post‐ vs pretreatment. Canonical pathway analysis using Ingenuity Pathway Analysis™ identified “role of nuclear factor of activated T‐cell in regulation of immune response” (Pnominal=1.35×10−5; PBH‐adjusted=4.79×10−3), “B‐cell development” (Pnominal=2.04×10−4; PBH‐adjusted=.024), “Fcγ receptor‐mediated phagocytosis in macrophages and monocytes” (Pnominal=2.04×10−4; PBH‐adjusted=.024) and “OX40 signalling” (Pnominal=2.82×10−4; PBH‐adjusted=.025) as pathways differentially regulated post‐ vs pretreatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL‐7 (P=2.28×10−6), TNF (P=4.26×10−6), Amyloid Precursor Protein (P=4.23×10−5) and SPI1/PI.1 (P=1.17×10−7). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56×10−7) and the quinoline alkaloid camptothecin (P=5.14×10−5). These results contribute to our understanding of immunopathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.

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Section: Discussionmentioning

confidence: 84%

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Salih

Fakiola

Lyons

et al. 2017

Parasite Immunology

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“…Recently, 8HQ derivatives have been reported as candidates to be developed as anti-gonorrhoeal agents including a multidrug resistant strain (ceftriaxone and cefixime resistances) (Lawung et al, 2018[ 13 ]). In addition, in vivo study of 8HQ and derivatives was documented as antileishmania agents in BALB/C mice (Duarte et al, 2016[ 9 ][ 8 ]).…”

Section: Discussionmentioning

confidence: 99%

Nitroxoline: a potent antimicrobial agent against multidrug resistant Enterobacteriaceae

Cherdtrakulkiat

Lawung

Nabu

et al. 2019

EXCLI Journal; 18:Doc445; ISSN 1611-2156

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“…Except in high doses, 8HQ is not known to exert toxicity in humans. Moreover, a recent study of 8HQ found low toxicity in murine peritoneal macrophages and no hemolytic activity in human red blood cells [36]. A preparation containing 8HQ was patented in 1989 as an oral antimicrobial agent (administered in feed or water) for use in poultry [37].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Selective Growth-Inhibitory Effect of 8-Hydroxyquinoline on Clostridium perfringens versus Bifidobacteria in a Medium Containing Chicken Ileal Digesta

et al. 2016

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Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16–32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32–2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry.

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An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis

Cited by 38 publications

References 54 publications

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Expression profiling of Sudanese visceral leishmaniasis patients pre‐ and post‐treatment with sodium stibogluconate

Nitroxoline: a potent antimicrobial agent against multidrug resistant Enterobacteriaceae

In Vitro Selective Growth-Inhibitory Effect of 8-Hydroxyquinoline on Clostridium perfringens versus Bifidobacteria in a Medium Containing Chicken Ileal Digesta

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