دورية أكاديمية
Discovery of Lead 2‑Thiazolylhydrazones with Broad-Spectrum and Potent Antifungal Activity
| العنوان: | Discovery of Lead 2‑Thiazolylhydrazones with Broad-Spectrum and Potent Antifungal Activity |
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| المؤلفون: | Nereu Junio Cândido Oliveira, Valtair Severino dos Santos Júnior, Isabella Campolina Pierotte, Victor Augusto Teixeira Leocádio, Luiz Felipe de Andrade Santana, Gabriel Vitor de Lima Marques, Ícaro Ferrari Protti, Saulo Fehelberg Pinto Braga, Markus Kohlhoff, Túlio Resende Freitas, Adriano de Paula Sabino, Thales Kronenberger, José Eduardo Gonçalves, Susana Johann, Daniel A. Santos, Isabela da Costa César, Vinícius Gonçalves Maltarollo, Renata Barbosa Oliveira |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Medicine, Microbiology, Pharmacology, Biotechnology, Evolutionary Biology, Ecology, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, novel antifungal agent, new therapeutical options, mic value ranging, invertebrate infection model, global health problem, obtain novel compounds, nine novel compounds, results obtained indicate, 2 cell model, 28 , synthesized compounds, potent compounds, vivo <, cryptococcus <, candida <, resistant yeast, permeability study, learning models, immunocompromised individuals, higher potency |
| الوصف: | Opportunistic fungal infections represent a global health problem, mainly for immunocompromised individuals. New therapeutical options are needed since several fungal strains show resistance to clinically available antifungal agents. 2-Thiazolylhydrazones are well-known as potent compounds against Candida and Cryptococcus species. A scaffold-focused drug design using machine-learning models was established to optimize the 2-thiazolylhydrazone skeleton and obtain novel compounds with higher potency, better solubility in water, and enhanced absorption. Twenty-nine novel compounds were obtained and most showed low micromolar MIC values against different species of Candida and Cryptococcus spp., including Candida auris, an emerging multidrug-resistant yeast. Among the synthesized compounds, 2-thiazolylhydrazone 28 (MIC value ranging from 0.8 to 52.17 μM) was selected for further studies: cytotoxicity evaluation, permeability study in Caco-2 cell model, and in vivo efficacy against Cryptococcus neoformans in an invertebrate infection model. All results obtained indicate the great potential of 28 as a novel antifungal agent. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Discovery_of_Lead_2_Thiazolylhydrazones_with_Broad-Spectrum_and_Potent_Antifungal_Activity/24774580Test |
| DOI: | 10.1021/acs.jmedchem.3c01105.s001 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.3c01105.s001Test https://figshare.com/articles/journal_contribution/Discovery_of_Lead_2_Thiazolylhydrazones_with_Broad-Spectrum_and_Potent_Antifungal_Activity/24774580Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.92DFB6E8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.3c01105.s001 |
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