Azoles containing naphthalene with activity against Gram-positive bacteria: in vitro studies and in silico predictions for flavohemoglobin inhibition

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dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridOzdemir, Zenyep/0000-0003-4559-2305
dc.authoridKocak Aslan, Ebru/0000-0003-0191-0746
dc.authorwosidKART, DIDEM/I-8446-2013
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidSARI, SUAT/A-5249-2017
dc.authorwosidSARI, SUAT/JCD-8070-2023
dc.authorwosidOzdemir, Zenyep/AAJ-6384-2020
dc.contributor.authorSari, Suat
dc.contributor.authorSabuncuoglu, Suna
dc.contributor.authorAslan, Ebru Kocak
dc.contributor.authorAvci, Ahmet
dc.contributor.authorKart, Didem
dc.contributor.authorOzdemir, Zeynep
dc.contributor.authorAcar, M. Fahir
dc.date.accessioned2024-08-04T20:50:22Z
dc.date.available2024-08-04T20:50:22Z
dc.date.issued2022
dc.departmentİnönü Üniversitesien_US
dc.description.abstractAzoles are first-line drugs used in fungal infections. Topical antifungals, such as miconazole and econazole, are known to be active against Gram-positive bacteria, which was reported to result from bacterial flavohemoglobin (flavoHb) inhibition. Dual antibacterial/antifungal action is believed to have benefits for antimicrobial chemotherapy. In this study, we tested antibacterial effects of an in-house library of naphthalene-bearing azoles, some of which were reported as potent antifungals, in an attempt to find dual-acting hits. Several potent derivatives were obtained against the Gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus. 9 was active at a minimum inhibitor concentration (MIC) less than 1 mg/ml against E. faecalis and S. aureus, and 10 against S. aureus. 16 was also potent against E. faecalis and S. aureus (MIC = 1 and 2 mg/ml, respectively). Six more were active against S. aureus with MIC <= 4 mg/ml. In vitro cytotoxicity studies showed that the active compounds were safe for healthy cells within their MIC ranges. According to the calculated descriptors, the library was found within the drug-like chemical space and free of pan-assay interference compounds (PAINS). Molecular docking studies suggested that the compounds might be bacterial flavohemoglobin (flavoHb) inhibitors and the azole and naphthalene rings were important pharmacophores, which was further supported by pharmacophore modeling study. As a result, the current study presents several non-toxic azole derivatives with antibacterial effects. In addition to their previously reported antifungal properties, they could set a promising starting point for the future design of dual acting antimicrobials.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [114S862]en_US
dc.description.sponsorshipThis work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) under Grant 114S862.en_US
dc.identifier.doi10.1080/07391102.2021.1940285
dc.identifier.endpage10229en_US
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.issue20en_US
dc.identifier.pmid34139139en_US
dc.identifier.scopus2-s2.0-85108329168en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage10220en_US
dc.identifier.urihttps://doi.org/10.1080/07391102.2021.1940285
dc.identifier.urihttps://hdl.handle.net/11616/99996
dc.identifier.volume40en_US
dc.identifier.wosWOS:000662838700001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.ispartofJournal of Biomolecular Structure & Dynamicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAzoleen_US
dc.subjectantibacterialen_US
dc.subjectStaphylococcus aureusen_US
dc.subjectEnterococcus faecalisen_US
dc.subjectflavohemoglobinen_US
dc.subjectcytotoxicityen_US
dc.subjectmolecular dockingen_US
dc.subjectpharmacophore modelingen_US
dc.titleAzoles containing naphthalene with activity against Gram-positive bacteria: in vitro studies and in silico predictions for flavohemoglobin inhibitionen_US
dc.typeArticleen_US

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