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dc.creatorLazić, Jelena O.
dc.creatorAjdačić, Vladimir
dc.creatorVojnović, Sandra
dc.creatorZlatović, Mario
dc.creatorPekmezović, Marina
dc.creatorMogavero, Selene
dc.creatorOpsenica, Igor
dc.creatorNikodinović-Runić, Jasmina
dc.date.accessioned2018-11-22T00:43:05Z
dc.date.available2018-11-22T00:43:05Z
dc.date.issued2018
dc.identifier.issn0175-7598
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/2078
dc.description.abstractCandida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.en
dc.publisherSpringer, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173048/RS//
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/642095/EU//
dc.relationEuropean Unions Horizon research and innovation program under the Marie Sklodowska-Curie Grant [642095]
dc.relationEuropean Society of Clinical Microbiology and Infectious Diseases (ESCMID)
dc.rightsrestrictedAccess
dc.sourceApplied Microbiology and Biotechnology
dc.subjectAntifungal activityen
dc.subjectCandida spp.en
dc.subjectBis-guanylhydrazoneen
dc.subjectDNA interactionen
dc.subjectROS generationen
dc.subjectSynergyen
dc.titleBis-guanylhydrazones as efficient anti-Candida compounds through DNA interactionen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПекмезовиц, Марина; Могаверо, Селене; Златовић, Марио; Војновиц, Сандра; Лазиц, Јелена; Aјдачић, Владимир; Опсеница, Игор; Никодиновић-Рунић, Јасмина;
dc.citation.volume102
dc.citation.issue4
dc.citation.spage1889
dc.citation.epage1901
dc.identifier.wos000424053700030
dc.identifier.doi10.1007/s00253-018-8749-3
dc.citation.other102(4): 1889-1901
dc.citation.rankM21
dc.identifier.pmid29330691
dc.description.otherSupplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3176]
dc.type.versionpublishedVersionen
dc.identifier.scopus2-s2.0-85041438337
dc.identifier.rcubKon_3409


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