Quinolinyl and quinolinyl N-oxide chalcones: Synthesis, antifungal and cytotoxic activities

Tavares, Luciana de Carvalho; Johann, Susana; Alves, Tânia Maria de Almeida; Guerra, Juliana C.; Souza-Fagundes, Elaine Maria de; Cisalpino, Patrícia Silva; Bortoluzzi, Adaı́lton J.; Caramori, Giovanni F.; Piccoli, Rafael de Mattos; Braibante, Hugo T. S.; Braibante, Mara Elisa Fortes; Pizzolatti, Moacir Geraldo

doi:10.1016/j.ejmech.2011.07.019

Cited by 43 publications

(9 citation statements)

References 41 publications

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“…Tests of susceptibility and MFC determination showed the potent action of 2-chalcone with a MIC of 7.8 mg/L in all tested strains. Although the action of chalcones varies widely with their structural replacement pattern, natural and synthetic chalcones have already shown antifungal activity against Candida spp ( Tavares et al., 2011 ), Cryptococcus gattii ( Palanco et al., 2017 ), Paracoccidioides brasiliensis ( Medina-Alarcón et al., 2020 ), H. capsulatum ( Melo et al., 2017 ), and against dermatophytes ( López et al., 2001 ; Gupta; Jain, 2015 ), proving to be potential candidates as future antifungal drugs. The MFC is defined as the lowest concentration of the drug necessary to inhibit 99.9% of fungal growth ( Gil-Alonso et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

Bila

Costa-Orlandi

Vaso

et al. 2021

Front. Cell. Infect. Microbiol.

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Dermatophytes, fungi that cause dermatophytosis, can invade keratinized tissues in humans and animals. The biofilm-forming ability of these fungi was described recently, and it may be correlated with the long treatment period and common recurrences of this mycosis. In this study, we evaluated the anti-dermatophytic and anti-biofilm activity of 2-hydroxychalcone (2-chalcone) in the dark and photodynamic therapy (PDT)-mediated and to determine its mechanism of action. Trichophyton rubrum and Trichophyton mentagrophytes strains were used in the study. The antifungal susceptibility test of planktonic cells, early-stage biofilms, and mature biofilms were performed using colorimetric methods. Topographies were visualized by scanning electron microscopy (SEM). Human skin keratinocyte (HaCat) monolayers were also used in the cytotoxicity assays. The mechanisms of action of 2-chalcone in the dark and under photoexcitation were investigated using confocal microscopy and the quantification of ergosterol, reactive oxygen species (ROS), and death induction by apoptosis/necrosis. All strains, in the planktonic form, were inhibited after treatment with 2-chalcone (minimum inhibitory concentration (MIC) = 7.8-15.6 mg/L), terbinafine (TRB) (MIC = 0.008–0.03 mg/L), and fluconazole (FLZ) (1–512 mg/L). Early-stage biofilm and mature biofilms were inhibited by 2-chalcone at concentrations of 15.6 mg/L and 31.2 mg/L in all tested strains. However, mature biofilms were resistant to all the antifungal drugs tested. When planktonic cells and biofilms (early-stage and mature) were treated with 2-chalcone-mediated PDT, the inhibitory concentrations were reduced by four times (2–7.8 mg/L). SEM images of biofilms treated with 2-chalcone showed cell wall collapse, resulting from a probable extravasation of cytoplasmic content. The toxicity of 2-chalcone in HaCat cells showed higher IC50 values in the dark than under photoexcitation. Further, 2-chalcone targets ergosterol in the cell and promotes the generation of ROS, resulting in cell death by apoptosis and necrosis. Overall, 2-chalcone-mediated PDT is a promising and safe drug candidate against dermatophytes, particularly in anti-biofilm treatment.

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Section: Discussionmentioning

confidence: 99%

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

Bila

Costa-Orlandi

Vaso

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Few studies have searched for new drugs from natural products for P. brasiliensis [17, 18]. There are reports of the activity of anti- Paracoccidioides of Piper regnellii and “ Baccharis dracunulifolia ” 30 mg/L [17, 19].…”

Section: Discussionmentioning

confidence: 99%

Antifungal Activity of Maytenin and Pristimerin

Gullo

Sardi

Santos

et al. 2012

Evidence-Based Complementary and Alternative Medicine

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Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents.

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“…lutzii , isolate Pb01). Searching for synthetic derivatives from chalcones (natural compounds) the lowest MIC value obtained was 1.9 μg/mL against isolate Pb18 [ 87 ]. When comparing the antifungal activity of F3307-0100 molecule with commercially available drugs, was observed that amphotericin B is 12 times more potent than the compounds obtained by virtual screening, on the other hand it has been associated with substantial toxicity and limitations [ 88 ], [ 89 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of New Antifungal Compounds Targeting Thioredoxin Reductase of Paracoccidioides Genus

Abadio¹,

Kioshima²,

Leroux³

et al. 2015

PLoS ONE

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The prevalence of invasive fungal infections worldwide has increased in the last decades. The development of specific drugs targeting pathogenic fungi without producing collateral damage to mammalian cells is a daunting pharmacological challenge. Indeed, many of the toxicities and drug interactions observed with contemporary antifungal therapies can be attributed to “nonselective” interactions with enzymes or cell membrane systems found in mammalian host cells. A computer-aided screening strategy against the TRR1 protein of Paracoccidioides lutzii is presented here. Initially, a bank of commercially available compounds from Life Chemicals provider was docked to model by virtual screening simulations. The small molecules that interact with the model were ranked and, among the best hits, twelve compounds out of 3,000 commercially-available candidates were selected. These molecules were synthesized for validation and in vitro antifungal activity assays for Paracoccidioides lutzii and P. brasiliensis were performed. From 12 molecules tested, 3 harbor inhibitory activity in antifungal assays against the two pathogenic fungi. Corroborating these findings, the molecules have inhibitory activity against the purified recombinant enzyme TRR1 in biochemical assays. Therefore, a rational combination of molecular modeling simulations and virtual screening of new drugs has provided a cost-effective solution to an early-stage medicinal challenge. These results provide a promising technique to the development of new and innovative drugs.

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Quinolinyl and quinolinyl N-oxide chalcones: Synthesis, antifungal and cytotoxic activities

Cited by 43 publications

References 41 publications

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

2-Hydroxychalcone as a Potent Compound and Photosensitizer Against Dermatophyte Biofilms

Antifungal Activity of Maytenin and Pristimerin

Identification of New Antifungal Compounds Targeting Thioredoxin Reductase of Paracoccidioides Genus

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