https://scholars.lib.ntu.edu.tw/handle/123456789/610516
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Juang, Yu-Pu | en_US |
dc.contributor.author | Chou, Yu-Ting | en_US |
dc.contributor.author | Lin, Ru-Xian | en_US |
dc.contributor.author | Ma, Hsiu-Hua | en_US |
dc.contributor.author | TAI-LING CHAO | en_US |
dc.contributor.author | Jan, Jia-Tsrong | en_US |
dc.contributor.author | SUI-YUAN CHANG | en_US |
dc.contributor.author | PI-HUI LIANG | en_US |
dc.date.accessioned | 2022-05-12T03:43:44Z | - |
dc.date.available | 2022-05-12T03:43:44Z | - |
dc.date.issued | 2022-05-05 | - |
dc.identifier.issn | 02235234 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/610516 | - |
dc.description.abstract | Niclosamide, a widely-used anthelmintic drug, inhibits SARS-CoV-2 virus entry through TMEM16F inhibition and replication through autophagy induction, but the relatively high cytotoxicity and poor oral bioavailability limited its application. We synthesized 22 niclosamide analogues of which compound 5 was found to exhibit the best anti-SARS-CoV-2 efficacy (IC50 = 0.057 μ M) and compounds 6, 10, and 11 (IC50 = 0.39, 0.38, and 0.49 μ M, respectively) showed comparable efficacy to niclosamide. On the other hand, compounds 5, 6, 11 contained higher stability in human plasma and liver S9 enzymes assay than niclosamide, which could improve bioavailability and half-life when administered orally. Fluorescence microscopy revealed that compound 5 exhibited better activity in the reduction of phosphatidylserine externalization compared to niclosamide, which was related to TMEM16F inhibition. The AI-predicted protein structure of human TMEM16F protein was applied for molecular docking, revealing that 4'-NO2 of 5 formed hydrogen bonding with Arg809, which was blocked by 2'-Cl in the case of niclosamide. | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | European journal of medicinal chemistry | en_US |
dc.subject | Entry inhibition; Niclosamide; SARS-CoV-2; Stability test; TMEM16F | en_US |
dc.title | Design, synthesis and biological evaluations of niclosamide analogues against SARS-CoV-2 | en_US |
dc.type | journal article | en_US |
dc.identifier.doi | 10.1016/j.ejmech.2022.114295 | - |
dc.identifier.pmid | 35344901 | - |
dc.identifier.scopus | 2-s2.0-85126980543 | - |
dc.identifier.url | https://scholars.lib.ntu.edu.tw/handle/123456789/604309 | - |
dc.relation.pages | 114295 | en_US |
dc.relation.journalvolume | 235 | en_US |
item.fulltext | no fulltext | - |
item.languageiso639-1 | en | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.cerifentitytype | Publications | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Laboratory Medicine-NTUH | - |
crisitem.author.dept | Pharmacy | - |
crisitem.author.dept | School of Pharmacy | - |
crisitem.author.orcid | 0000-0002-9815-6702 | - |
crisitem.author.orcid | 0000-0002-6009-6724 | - |
crisitem.author.orcid | 0000-0001-6668-4642 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學檢驗暨生物技術學系 |
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