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Ivanov Marija - One of the best experts on this subject based on the ideXlab platform.
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Flavones, flavonols, and glycosylated derivatives—impact on candida albicans growth and virulence, expression of cdr1 and erg11, cytotoxicity
'MDPI AG', 2021Co-Authors: Ivanov Marija, Kannan Abhilash, Stojković, Dejan S., Glamočlija Jasmina, Calhelha, Ricardo C., Ferreira, Isabel C.f.r., Sanglard Dominique, Soković MarinaAbstract:Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and Apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxi-city of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, Apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except Apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and Apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy.This research is funded by the Serbian Ministry of Education, Science and Technological Development [Contract No. 451-03-68/2020-14/200007]. The authors are grateful to the FEMS for providing FEMS Research and Training Grant [FEMS-GO-2017-015] to Marija Ivanov for her visit to Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Rue du Bugnon 48, Lausanne, Switzerland. The authors are also grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO [UIDB/00690/2020] and to the national funding by FCT, P.I., through the institutional scientific employment program-contract for R. Calhelha’s contract.info:eu-repo/semantics/publishedVersio
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Mechanisms by which selected flavonoids, terpenes and nitrate esters of heterocyclic compounds exert activity towards Candida albicans strains isolated from the human oral cavity
Belgrade: Faculty of Biology University of Belgrade, 2019Co-Authors: Ivanov MarijaAbstract:Vrsta Candida albicans jedan je od najčešćih uzročnika gljivičnih infekcija ljudi. U okviru ove doktorske disertacije ispitivani su mehanizmi antifungalnog delovanja 9 flavonoida (apigenin, Apigetrin, astragalin, kvercetin, kvercitrin, izokvercitrin, rutin, luteolin i viteksin), 2 terpena (kamfor i eukaliptol) i 4 nitratna estra heterocikličnih jedinjenja (N-(2-nitrooksietil)-1Η-indol-2-karboksamid (MK55), Ν-(2-nitroksietil)-hinolin-2-karboksamid (MK56), Ν-(2-nitroksietil)-6-(piperidin-1-il)-9H-purin acetamid (MK94), 5΄-Ο-nitro adenozin (MK129)). Najbolju antifungalnu aktivnost ispoljili su nitratni estri heterocikličnih jedinjenja. U smanjenju razvoja virulentnosti ove gljive, nastanku biofilma i formiranju hifalnih ćelija, istakla se aktivnost flavonoida, posebno Apigetrina, apigenina i izokvercitrina. Razvoj antifungalne rezistencije C. albicans povezan je sa povećanjem aktivnosti efluks pumpi kodiranih genima MDR1, CDR1 i CDR2. Promene u ekspresiji ovih gena zabeležene su nakon tretmana astragalinom i apigeninom (smanjenje ekspresije CDR1), kamforom (povećanje ekspresije CDR1, smanjenje ekspresije CDR2) i eukaliptolom (povećanje ekspresije CDR1 i CDR2), ukazujući na potencijalna korisna svojstva flavonoida, ali i moguće neželjene posledice primene testiranih terpena. Rezistencija je povezana i sa povećanom ekspresijom ERG11, gena koji kodira protein lanosterol 14α-demetilazu (CYP51), ciljno mesto azolnih lekova. Izokvercitrin i MK94 izazivaju neželjeno povećanje, dok MK55 redukuje nivo ekspresije ovog gena. Mehanizam antifungalnog delovanja MK55 obuhvata i inhibiciju fungalnog proteina CYP51. Narušavanje integriteta ćelijske membrane, kao potencijalnog mehanizma delovanja, potvrđeno je za apigenin, Apigetrin i astragalin. Upotreba MK55, MK94, apigenina, Apigetrina, rutina, kvercetina, kvercitrina, izokvercitrina, luteolina i kamfora može se smatrati bezbednom, dok se eukaliptol zbog svog citotoksičnog efekta prema ćelijama jetre ne preporučuje za potencijalnu primenu u antifungalnoj terapiji.Candida albicans is among the most common human fungal pathogens. Mode of antifungal action has been tested for 9 flavonoids (apigenin, Apigetrin, astragalin, quercetin, quercitrin, isoquercitrin, rutin, luteolin and vitexin), 2 terpens (camphor and eucalyptol) and 4 nitrate esters of heterocyclic compounds (N-(2-nitooxyethyl)-1Η-indol-2-carboxamide (MK55), Ν-(2-nitrooxyethyl)-quinoline-2-carboxamide (MK56), Ν-(2-nitrooxyethyl)-6-(piperidin-1-yl)-9H-purine acetamide (MK94), 5΄-Ο-nitroadenosine (MK129)). The most prominent anticandidal activity has been proven for nitrate esters of heterocyclic compounds. Significant activity of flavonoids, especially Apigetrin, apigenin and isoquercitrin, could be noticed in reducing fungal virulence, biofilm formation and hyphal growth. Resistance to antifungal therapy is linked to increased activity of C. albicans efflux pumps encoded by MDR1, CDR1 and CDR2. Disturbance in expression levels of these genes has been observed after treatment with astragalin and apigenin (decreased CDR1 expression), camphor (increased CDR1 and decreased CDR2 expression) and eucalyptol (increased CDR1 and CDR2 expression levels), suggesting possible beneficial antimicrobial effects of flavonoids as well as potential harmful consequences of selected terpenes application. Antifungal resistance is also linked to increased expression of ERG11, gene encoding for lanosterol 14α-demethylase (CYP51), target protein for azole antifungals. Treatment with isoquercitrin and MK94 led to increased expression of this gene, while treatment with MK55 reduced it. Mode of action for MK55 involves inhibition of CYP51 enzyme. Damage of fungal cell membrane as a potential mechanism of antifungal activity has been observed for apigenin, Apigetrin and astragalin. Application of MK55, MK94, apigenin, Apigetrin, rutin, quercetin, quercitrin, isoquercitrin, luteolin and camphor could be considered safe, based on the results of their cytotoxicity towards the liver cell line, while eucalyptol should be used with serious precaution
Soković M. - One of the best experts on this subject based on the ideXlab platform.
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Flavones, Flavonols, and Glycosylated Derivatives-Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity.
'MDPI AG', 2020Co-Authors: Ivanov M., Kannan A., Stojković D.s., Glamočlija J., Calhelha R.c., Ferreira Icfr, Sanglard D., Soković M.Abstract:Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and Apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, Apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except Apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and Apigetrin; these results indicate flavonoids' indispensable capacity for further development as part of an anticandidal therapy or prevention strategy
Soković Marina - One of the best experts on this subject based on the ideXlab platform.
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Flavones, flavonols, and glycosylated derivatives—impact on candida albicans growth and virulence, expression of cdr1 and erg11, cytotoxicity
'MDPI AG', 2021Co-Authors: Ivanov Marija, Kannan Abhilash, Stojković, Dejan S., Glamočlija Jasmina, Calhelha, Ricardo C., Ferreira, Isabel C.f.r., Sanglard Dominique, Soković MarinaAbstract:Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and Apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxi-city of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, Apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except Apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and Apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy.This research is funded by the Serbian Ministry of Education, Science and Technological Development [Contract No. 451-03-68/2020-14/200007]. The authors are grateful to the FEMS for providing FEMS Research and Training Grant [FEMS-GO-2017-015] to Marija Ivanov for her visit to Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Rue du Bugnon 48, Lausanne, Switzerland. The authors are also grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO [UIDB/00690/2020] and to the national funding by FCT, P.I., through the institutional scientific employment program-contract for R. Calhelha’s contract.info:eu-repo/semantics/publishedVersio
Ivanov M. - One of the best experts on this subject based on the ideXlab platform.
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Flavones, Flavonols, and Glycosylated Derivatives-Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity.
'MDPI AG', 2020Co-Authors: Ivanov M., Kannan A., Stojković D.s., Glamočlija J., Calhelha R.c., Ferreira Icfr, Sanglard D., Soković M.Abstract:Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and Apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, Apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except Apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and Apigetrin; these results indicate flavonoids' indispensable capacity for further development as part of an anticandidal therapy or prevention strategy
Kannan A. - One of the best experts on this subject based on the ideXlab platform.
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Flavones, Flavonols, and Glycosylated Derivatives-Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity.
'MDPI AG', 2020Co-Authors: Ivanov M., Kannan A., Stojković D.s., Glamočlija J., Calhelha R.c., Ferreira Icfr, Sanglard D., Soković M.Abstract:Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and Apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, Apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except Apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and Apigetrin; these results indicate flavonoids' indispensable capacity for further development as part of an anticandidal therapy or prevention strategy