دورية أكاديمية
Chloride substitution on 2-hydroxy-3,4,6-trimethoxyphenylchalcones improves in vitro selectivity on Trypanosoma cruzi strain Y.
| العنوان: | Chloride substitution on 2-hydroxy-3,4,6-trimethoxyphenylchalcones improves in vitro selectivity on Trypanosoma cruzi strain Y. |
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| المؤلفون: | Magalhães EP; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil., Gomes NDB; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil., Freitas TA; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil., Silva BP; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil., Ribeiro LR; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil., Ameida-Neto FWQ; Department of Analytical Chemistry and Physical Chemistry, Science Center, Federal University of Ceará, Campus do Pici, Fortaleza, CE, Brazil., Marinho MM; Iguatu Faculty of Education, Science and Letters, State University of Ceará, Iguatu, CE, Brazil., Lima-Neto P; Department of Analytical Chemistry and Physical Chemistry, Science Center, Federal University of Ceará, Campus do Pici, Fortaleza, CE, Brazil., Marinho ES; Theoretical and Electrochemical Chemistry Research Group, State University of Ceará, Limoeiro do Norte, CE, Brazil., Santos HSD; State University of Vale do Acaraú, Center for Exact Sciences and Technology, Sobral, CE, Brazil., Teixeira AMR; Regional University of Cariri, Department of Biological Chemistry, Crato, CE, Brazil., Sampaio TL; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, CE, Brazil., Menezes RRPPB; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: ramonppessoa@ufc.br., Martins AMC; Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Clinical and Toxicological Analysis, Federal University of Ceará, Fortaleza, CE, Brazil. |
| المصدر: | Chemico-biological interactions [Chem Biol Interact] 2022 Jul 01; Vol. 361, pp. 109920. Date of Electronic Publication: 2022 Apr 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| مواضيع طبية MeSH: | Chagas Disease*/drug therapy , Chalcone*/pharmacology , Chalcones*/pharmacology , Chalcones*/therapeutic use , Trypanocidal Agents*/pharmacology , Trypanosoma cruzi*, Chlorides/pharmacology ; Chlorine ; Humans ; Molecular Docking Simulation |
| مستخلص: | Chagas disease is a disease that is emerging in North America and Europe countries. Benznidazole is the main drug available, but it has high toxicity and low efficacy in the chronic phase. In this way, researching new antichagasic agents is necessary. Thus, the aim of this study is to evaluate the effect of novel chalcones and the influence of chlorine substitutions on Trypanosoma cruzi and host cells. Unsubstituted (1), 4-chlorine substituted (2) and 2,4-chlorine substituted (3) chalcones were synthesized by Claisen-Schmidt condensation, characterized, and electrical distribution was assessed by Density Fuctional Theory (DFT). The host cells toxicity (LLC-MK2) was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) reduction assay. The effect on epimastigote (24, 48 and 72h), trypomastigote (24h) and amastigotes (24 h) was evaluated. Flow cytometry assays were performed with 7-Aminoactinomycin D (7-AAD) and Annexin-PE, Dichlorofluorescein diaceteate (DCFH-DA) and Rhodamine123 (Rho123). Finally, molecular docking predicted interactions between chalcones and cruzain (TcCr) and trypanothione reductase (TcTR). The toxicity on host cells was reduced almost twenty times on chlorine substituted molecules. On epimastigote and trypomastigote forms, all substances presented similar effects. After treatment with molecule 3, it was observed a decrease in infected cells and intracellular amastigotes. Their effect is related to necrotic events, increase of cytoplasmic Reactive Oxygen Species (ROS) and mitochondrial dysfunction. Also, this effect might be associated with involvement of TcCr and TcTR enzymes. Therefore, the results showed that chlorine substitution on chalcones reduces the host cell's toxicity without compromising the effect on Trypanosoma cruzi Y strain forms, and it occurs over membrane damage, oxidative stress and possible interactions with TcCr and TcTR. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Chagas disease; Chalcones; Cruzain; Trypanothione reductase |
| المشرفين على المادة: | 0 (Chalcones) 0 (Chlorides) 0 (Trypanocidal Agents) 4R7X1O2820 (Chlorine) 5S5A2Q39HX (Chalcone) |
| تواريخ الأحداث: | Date Created: 20220424 Date Completed: 20220530 Latest Revision: 20220530 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.cbi.2022.109920 |
| PMID: | 35461787 |
| قاعدة البيانات: | MEDLINE |
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