Design, synthesis and anti‐influenza virus activity of 4‐tert‐butyl‐n‐(3‐oxo‐1‐thia‐4‐azaspiro[4.5]dec‐4‐yl) benzamide derivatives that target hemagglutinin‐mediated fusion

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dc.authorid0000-0002-0309-663X
dc.authorid0000-0001-8875-3522
dc.authorid0000-0001-9742-9302
dc.authorid0000-0003-0516-6010
dc.contributor.authorÇınar, Gözde
dc.contributor.authorAlikadıoğlu, Zeynep
dc.contributor.authorSoylu Eter, Özge
dc.contributor.authorNaesens, Lieve
dc.contributor.authorCihan Üstündağ, Gökçe
dc.date.accessioned2025-03-28T07:46:04Z
dc.date.available2025-03-28T07:46:04Z
dc.date.issued2025
dc.departmentFakülteler, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.description.abstractHemagglutinin (HA) is a viral glycoprotein that mediates influenza virus entry into the host cell and is considered a relevant viral target. We here report the identification of a class of 4‐tert‐butylphenyl‐substituted spirothiazolidinones as HA‐mediated fusion inhibitors with specific activity against influenza A/H3N2 virus. The novel spirocyclic compounds were achieved by using one‐pot cyclocondensation method and the chemical structures were characterized by IR, 1 H NMR, 13C NMR, and elemental analysis. Compound 2c, bearing methyl substitutions at positions 2‐ and 8‐ of the spiro ring displayed an EC50 value against influenza A/H3N2 virus of 1.3 μM and an antiviral selectivity index of 30. The fusion‐inhibiting effect of compound 2c was revealed in the polykaryon assay which is based on cell‐cell fusion when influenza virus H3 HA‐transfected cells are exposed to low pH. Computer‐aided docking was performed to predict the possible binding pocket in the H3 HA trimer. Resistance data and in silico studies indicated that compound 2c has an overlapping binding pocket in the stem region of H3 HA with the known fusion inhibitors TBHQ and arbidol.
dc.description.sponsorshipWe would like to thank Professor Gültaze Çapan for sharing expertize in medicinal chemistry. L.N. wishes to thank the team of L. Persoons for dedicated technical assistance. This workstudy was supported by Scientific Research Projects Coordination Unit of Istanbul University (Grant Number: 32246).
dc.identifier.citationÇınar, G., Alikadıoğlu, Z., Soylu Eter, Ö., Naesens, L., & Cihan Üstündağ, G. (2025). Design, synthesis and anti‐influenza virus activity of 4‐tert‐butyl‐n‐(3‐oxo‐1‐thia‐4‐azaspiro[4.5]dec‐4‐yl) benzamide derivatives that target hemagglutinin‐mediated fusion. Drug Development Research, pp. 1-15. https://doi.org/10.1002/ddr.70080
dc.identifier.doi10.1002/ddr.70080
dc.identifier.endpage15
dc.identifier.issn1098-2299
dc.identifier.issn0272-4391
dc.identifier.pmid40125625
dc.identifier.scopusqualityQ2
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1002/ddr.70080
dc.identifier.urihttps://hdl.handle.net/20.500.13055/946
dc.identifier.wosqualityQ2
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorÇınar, Gözde
dc.institutionauthorid0000-0002-0309-663X
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofDrug Development Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectAntiviral
dc.subjectHemagglutinin
dc.subjectİnfluenza Virus
dc.subjectSpirothiazolidinone
dc.subjectSynthesis
dc.titleDesign, synthesis and anti‐influenza virus activity of 4‐tert‐butyl‐n‐(3‐oxo‐1‐thia‐4‐azaspiro[4.5]dec‐4‐yl) benzamide derivatives that target hemagglutinin‐mediated fusion
dc.typeArticle
dspace.entity.typePublication

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