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Synthesis and structure-activity relationship of L-methionine-coupled 1,3,4-thiadiazole derivatives with activity against influenza virus

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dc.contributor.authorTATAR, ESRA
dc.contributor.authorsTatar, Esra; Yaldiz, Seda; Kulabas, Necla; Vanderlinden, Evelien; Naesens, Lieve; Kucukguzel, Ilkay
dc.date.accessioned2022-03-12T22:56:14Z
dc.date.available2022-03-12T22:56:14Z
dc.description.abstractIn previous investigations, we identified a class of 1,3,4-thiadiazole derivatives with antiviral activity. N-{3-(Methylsulfanyl)-1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide emerged as a relevant lead compound for designing novel influenza A virus inhibitors. In the present study, we elaborated on this initial lead by performing chemical synthesis and antiviral evaluation of a series of structural analogues. During this research, thirteen novel 1,3,4-thiadiazole derivatives were synthesized by the cyclization of the corresponding thiosemicarbazides as synthetic precursors. The structures and the purities of the synthesized compounds were confirmed through chromatographic and spectral data. Four L-methionine-based 1,3,4-thiadiazole derivatives displayed activity against influenza A virus, the two best compounds being 24 carrying a 5-(4-chlorophenylamino)-1,3,4-thiadiazole moiety and 30 possessing a 5-(benzoylamino)-1,3,4-thiadiazole structure [antiviral EC50 against influenza A/H3N2 virus: 4.8 and 7.4 mu M, respectively]. The 1,3,4-thiadiazole derivatives were inactive against influenza B virus and a wide panel of unrelated DNA and RNA viruses. Compound 24 represents a new class of selective influenza A virus inhibitors acting during the virus entry process, as evidenced by our findings in a time-of-addition assay. Molecular descriptors and in silico prediction of ADMET properties of the active compounds were calculated. According to in silico ADMET and drug similarity studies, active compounds have been estimated to be good candidates for oral administration with no apparent toxicity considerations.
dc.identifier.doi10.1111/cbdd.13995
dc.identifier.eissn1747-0285
dc.identifier.issn1747-0277
dc.identifier.pubmed34873848
dc.identifier.urihttps://hdl.handle.net/11424/236911
dc.identifier.wosWOS:000729319600001
dc.language.isoeng
dc.publisherWILEY
dc.relation.ispartofCHEMICAL BIOLOGY & DRUG DESIGN
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subject1
dc.subject3
dc.subject4-thiadiazoles
dc.subjectADMET
dc.subjectantiviral activity
dc.subjectinfluenza virus
dc.subjectL-methionine
dc.subjectvirus entry
dc.subjectDRUG DISCOVERY
dc.subjectNONNUCLEOSIDE INHIBITORS
dc.subjectSCREENING LIBRARIES
dc.subjectANTITUBERCULOSIS
dc.subjectREPLICATION
dc.subjectSTRATEGIES
dc.subjectPREDICTION
dc.subjectDESIGN
dc.subjectHIV
dc.subject4-THIAZOLIDINONES
dc.titleSynthesis and structure-activity relationship of L-methionine-coupled 1,3,4-thiadiazole derivatives with activity against influenza virus
dc.typearticle
dspace.entity.typePublication
local.avesis.id0ce99b06-7b09-4b40-a98e-9b2e211999bc
local.import.packageSS17
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages18
oaire.citation.titleCHEMICAL BIOLOGY & DRUG DESIGN
relation.isAuthorOfPublicatione2c939bf-1387-4174-802c-e714419b20af
relation.isAuthorOfPublication.latestForDiscoverye2c939bf-1387-4174-802c-e714419b20af

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