Antioxidant Activity of New Benzo[de]quinolines and Lactams: 2DQuantitative Structure-Activity Relationships

Ghinet, Alina; Farce, Amaury; Oudir, Souhila; Pommery, Jean; Vamecq, Jòseph; Hénichart, Jean‐Pierre; Rigo, Benoı̂t; Gautret, Philippe

doi:10.2174/157340612802084216

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…Analogs of the quinoline ring derivative berbamine have also recently been shown to block uptake of aminoglycosides into hair cells; however, the degree of uptake block did not correlate with the magnitude of hair-cell protection from aminoglycosides, suggesting a second uptake-independent mechanism (Kruger et al, 2016;Hudson et al, 2020). Quinoline ring derivatives have been shown to have antioxidant properties in other systems (Detsi et al, 2007;Naik et al, 2009;Ghinet et al, 2012). It would be interesting to know whether these compounds also function as antioxidants in a zebrafish or mammalian model of ototoxicity, as it will be important to identify drugs that could target both aminoglycoside uptake and oxidative stress in hair cells as candidate treatments for the prevention of aminoglycoside-induced hearing loss in humans.…”

Section: Mitochondrial Ros Production and Antioxidant Protection Agai...mentioning

confidence: 99%

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

Holmgren

Sheets

2021

Front. Cell Dev. Biol.

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Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model in which to study hair-cell mitochondrial activity. Moreover, the ease of genetic manipulation of zebrafish embryos allows for the study of mutations implicated in human deafness, as well as the generation of transgenic models to visualize mitochondrial calcium transients and mitochondrial activity in live organisms. Studies of the zebrafish lateral line have shown that variations in mitochondrial activity can predict hair-cell susceptibility to damage by aminoglycosides or noise exposure. In addition, antioxidants have been shown to protect against noise trauma and ototoxic drug–induced hair-cell death. In this review, we discuss the tools and findings of recent investigations into zebrafish hair-cell mitochondria and their involvement in cellular processes, both under homeostatic conditions and in response to noise or ototoxic drugs. The zebrafish lateral line is a valuable model in which to study the roles of mitochondria in hair-cell pathologies and to develop therapeutic strategies to prevent sensorineural hearing loss in humans.

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Section: Mitochondrial Ros Production and Antioxidant Protection Agai...mentioning

confidence: 99%

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

Holmgren

Sheets

2021

Front. Cell Dev. Biol.

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“…It is worth noting that quinoline derivatives have been noted to have some antioxidant properties in other systems (Detsi et al 2007;Naik et al 2009;Ghinet et al 2012) although this has not been examined in hair cells.…”

Section: All Of the Protective Quinoline Derivatives Reduce Gttr Uptakementioning

confidence: 99%

Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Keating

et al. 2012

JARO

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We have previously published results from a screen of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection) for drugs that protect against neomycin-induced hair cell death (Ou et al., J Assoc Res Otolaryngol 10:191-203, 2009). Further evaluation of this drug library identified eight protective drugs that shared a common quinoline scaffold. These drugs were tested further in terms of their protection against other aminoglycosides, as well as their effect on aminoglycoside uptake. All of the eight quinolines that protected against neomycin were found to protect against shortand long-term gentamicin damage protocols. We then tested the structurally related compounds quinoline, isoquinoline, naphthalene, and indole for protective effects. Of these compounds, indole demonstrated a small but significant amount of protection against neomycin, while quinoline and isoquinoline partially protected against long-term gentamicin damage. We examined whether the protective activity of this group of compounds was related to known targets of the quinoline derivatives. The protective effects did not seem linked to either the cholinergic or histaminergic pathways that are regulated by some members of the quinoline family. However, all eight protective drugs were found to reduce the uptake of aminoglycosides into hair cells. Subsequent experiments suggest that reduction of uptake is the primary mechanism of protection among the quinoline drugs.

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“…Since antoxidant activities of these chemicals depends on their structures, it was therefore possible to predict the antioxidant activities of the compounds of interest from their structural features using the quantitative structure–activity relationship (QSAR) approach. QSAR methodology has often been used to find correlations between activity and molecular structural descriptors of different classes of chemicals. , There are some published reports about QSAR prediction of antioxidant activities of some organic compound. − For example, R. M. V. Abreu et al have built a QSAR model for description and prediction of the radical scavenging activity of di(hetero)arylamine derivatives of benzo[b]thiophenes using the partial least-squares (PLS) projection of the latent structures method, which gives the statistical parameters of R 2 = 0.881 and q 2 LOO = 0.844 . In another report, K. Roy et al utilize a series of coumarin derivatives that were modeled for their antioxidant activities based on their ability to inhibit DPPH (1,1-diphenyl-2-picryl-hydrazyl) free radicals.…”

Section: Introductionmentioning

confidence: 99%

Prediction of the Radical Scavenging Activities of Some Antioxidant from Their Molecular Structure

Fatemi

Rostami

2013

Ind. Eng. Chem. Res.

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Quantitative structure–activity relationships (QSAR) studies were performed on the radical scavenging activities of a set of compounds consisting of various types of antioxidant families. The predicting five parameter models correlating selected descriptors, derived from the 2D and 3D representations of molecules and antioxidant activity, were set up using multiple linear regressions (MLR) and a multilayer perceptron neural network (MLP-NN), separately. The best obtained model had statistics of R 2 = 0.968 and q 2 = 0.898 for the MLP-NN model and R 2 = 0.902 and q 2 = 0.862 for the MLR model. The chemical applicability domains of these models were determined via a leverage approach. The obtained result indicated that the proposed models can be successfully used for predictions of radical scavenging activities of new antioxidants.

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Antioxidant Activity of New Benzo[de]quinolines and Lactams: 2DQuantitative Structure-Activity Relationships

Cited by 5 publications

References 22 publications

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

Using the Zebrafish Lateral Line to Understand the Roles of Mitochondria in Sensorineural Hearing Loss

Quinoline Ring Derivatives Protect Against Aminoglycoside-Induced Hair Cell Death in the Zebrafish Lateral Line

Prediction of the Radical Scavenging Activities of Some Antioxidant from Their Molecular Structure

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