Anti-amoebic effects of synthetic acridine-9(10H)-one against brain-eating amoebae

dc.authoridKhan, Naveed/0000-0001-7667-8553;
dc.authorwosidKhan, Naveed/AAM-2892-2021
dc.authorwosidKhan, Naveed/KCK-0156-2024
dc.contributor.authorAhmed, Usman
dc.contributor.authorManzoor, Mehwish
dc.contributor.authorQureshi, Sehrish
dc.contributor.authorMazhar, Muzna
dc.contributor.authorFatima, Arj
dc.contributor.authorAurangzeb, Sana
dc.contributor.authorHamid, Mehwish
dc.date.accessioned2024-05-19T14:45:55Z
dc.date.available2024-05-19T14:45:55Z
dc.date.issued2023
dc.departmentİstinye Üniversitesien_US
dc.description.abstractPathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 mu g/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 mu g/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 mu g/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.en_US
dc.identifier.doi10.1016/j.actatropica.2023.106824
dc.identifier.issn0001-706X
dc.identifier.issn1873-6254
dc.identifier.pmid36610529en_US
dc.identifier.scopus2-s2.0-85147457418en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org10.1016/j.actatropica.2023.106824
dc.identifier.urihttps://hdl.handle.net/20.500.12713/5392
dc.identifier.volume239en_US
dc.identifier.wosWOS:000922486900001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofActa Tropicaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240519_kaen_US
dc.subjectNen_US
dc.subjectFowlerien_US
dc.subjectIn Silicoen_US
dc.subjectCysteine Proteaseen_US
dc.subjectCathepsin B Proteaseen_US
dc.titleAnti-amoebic effects of synthetic acridine-9(10H)-one against brain-eating amoebaeen_US
dc.typeArticleen_US

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