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Studies of Cytotoxicity Effects, SARS-CoV-2 Main Protease Inhibition, and in Silico Interactions of Synthetic Chalcones.

التفاصيل البيبلوغرافية
العنوان: Studies of Cytotoxicity Effects, SARS-CoV-2 Main Protease Inhibition, and in Silico Interactions of Synthetic Chalcones.
المؤلفون: Guterres Fernandes OL; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil., Tizziani T; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil., Dambrós BP; Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil., Ferreira de Sousa N; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Universidade Federal de Paraíba, 50670-910, João Pessoa, Paraíba, Brazil., Mansur Pontes CL; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil., da Silva LAL; Postgraduate Program in Pharmacy, Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900, Florianópolis, SC, Brazil., Escorteganha Pollo LA; Postgraduate Program in Pharmacy, Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900, Florianópolis, SC, Brazil., de Assis FF; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil., Scotti MT; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Universidade Federal de Paraíba, 50670-910, João Pessoa, Paraíba, Brazil., Scotti L; Postgraduate Program in Natural and Bioactive Synthetic Products, Department of Pharmaceutical Sciences, Universidade Federal de Paraíba, 50670-910, João Pessoa, Paraíba, Brazil., Braga AL; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil., Steindel M; Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Santa Catarina, Brazil., Sandjo LP; Postgraduate Program in Chemistry, Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário da Trindade, 88040-900, Florianópolis, SC, Brazil.
المصدر: Chemistry & biodiversity [Chem Biodivers] 2023 Mar; Vol. 20 (3), pp. e202201151. Date of Electronic Publication: 2023 Feb 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Verlag Helvetica Chimica Acta Country of Publication: Switzerland NLM ID: 101197449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1612-1880 (Electronic) Linking ISSN: 16121872 NLM ISO Abbreviation: Chem Biodivers Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Zürich, Switzerland : Hoboken, NJ : Verlag Helvetica Chimica Acta ; Distributed in the USA by Wiley, c2004-
مواضيع طبية MeSH: COVID-19* , Chalcones*/pharmacology , Chalcones*/chemistry, Humans ; SARS-CoV-2 ; Molecular Docking Simulation ; Protease Inhibitors/pharmacology ; Protease Inhibitors/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; Molecular Dynamics Simulation
مستخلص: SARS-CoV-2 main protease (M pro ) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against M pro of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with IC 50 ranging from 13.76 and 36.13 μM. Except for 35 and 36, other active compounds were not cytotoxic up to 150 μM against THP-1 and Vero cell lines. Compounds 10, and 35-39 showed no hemolysis while 28 was weakly hemotoxic at 150 μM. Moreover, molecular docking showed interactions between compound 10 and M pro (PDBID 5RG2 and 5RG3) with proximity to cys145 and His41, suggesting a covalent binding. Products of the reaction between chalcones and cyclohexanethiol indicated that this binding could be a Michael addition type.
(© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
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معلومات مُعتمدة: 633/2020 CAPES; 306653/2020-6 CNPq
فهرسة مساهمة: Keywords: SARS-CoV-2 Mpro; heterocyclic chalcones; inhibitory effects; molecular docking
المشرفين على المادة: 0 (Chalcones)
EC 3.4.22.- (3C-like proteinase, SARS-CoV-2)
0 (Protease Inhibitors)
0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20230205 Date Completed: 20230324 Latest Revision: 20230324
رمز التحديث: 20231215
DOI: 10.1002/cbdv.202201151
PMID: 36740573
قاعدة البيانات: MEDLINE
الوصف
تدمد:1612-1880
DOI:10.1002/cbdv.202201151