دورية أكاديمية
Computer-Aided drug design of new 2-amino-thiophene derivatives as anti-leishmanial agents.
| العنوان: | Computer-Aided drug design of new 2-amino-thiophene derivatives as anti-leishmanial agents. |
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| المؤلفون: | Luna IS; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB, Brazil; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB, Brazil., Souza TA; Multiuser Laboratory Center of Characterization and Analysis, Federal University of Paraiba, João Pessoa, PB, Brazil., da Silva MS; Multiuser Laboratory Center of Characterization and Analysis, Federal University of Paraiba, João Pessoa, PB, Brazil., Franca Rodrigues KAD; Infectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba, PI, Brazil., Scotti L; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB, Brazil., Scotti MT; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB, Brazil., Mendonça-Junior FJB; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, João Pessoa, PB, Brazil; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, PB, Brazil. Electronic address: franciscojaime@servidor.uepb.edu.br. |
| المصدر: | European journal of medicinal chemistry [Eur J Med Chem] 2023 Mar 15; Vol. 250, pp. 115223. Date of Electronic Publication: 2023 Feb 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| مواضيع طبية MeSH: | Antiprotozoal Agents*/chemistry , Leishmania* , Leishmaniasis*/drug therapy , Leishmaniasis*/parasitology, Humans ; Thiophenes/pharmacology ; Thiophenes/therapeutic use ; Drug Design |
| مستخلص: | The leishmaniasis is a neglected disease caused by a group of protozoan parasites from the genus Leishmania whose treatment is limited, obsolete, toxic, and ineffective in certain cases. These characteristics motivate researchers worldwide to plan new therapeutic alternatives for the treatment of leishmaniasis, where the use of cheminformatics tools applied to computer-assisted drug design has allowed research to make great advances in the search for new drugs candidates. In this study, a series of 2-amino-thiophene (2-AT) derivatives was screened virtually using QSAR tools, ADMET filters and prediction models, allowing direct the synthesis of compounds, which were evaluated in vitro against promastigotes and axenic amastigotes of Leishmania amazonensis. The combination of different descriptors and machine learning methods led to obtaining robust and predictive QSAR models, which was obtained from a dataset composed of 1862 compounds extracted from the ChEMBL database, with correct classification rates ranging from 0.53 (for amastigotes) to 0.91 (for promastigotes), allowing to select eleven 2-AT derivatives, which do not violate Lipinski's rules, exhibit good druglikeness, and with probability ≤70% of potential activity against the two evolutionary forms of the parasite. All compounds were properly synthesized and 8 of them were shown to be active at least against one of the evolutionary forms of the parasite with IC Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Masson SAS. All rights reserved.) |
| فهرسة مساهمة: | Keywords: 2-Amino-thiophene; Computer-aided drug design; Neglected diseases; Virtual screening, anti-leishmanial |
| المشرفين على المادة: | 0 (Antiprotozoal Agents) 0 (Thiophenes) |
| تواريخ الأحداث: | Date Created: 20230227 Date Completed: 20230315 Latest Revision: 20230315 |
| رمز التحديث: | 20230315 |
| DOI: | 10.1016/j.ejmech.2023.115223 |
| PMID: | 36848847 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2023.115223 |