دورية أكاديمية
In silico-chemogenomic repurposing of new chemical scaffolds for histoplasmosis treatment.
| العنوان: | In silico-chemogenomic repurposing of new chemical scaffolds for histoplasmosis treatment. |
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| المؤلفون: | Santos AS; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil., Borges Dos Anjos LR; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil., Costa VAF; Laboratory of Cheminformatics (LabChem), Faculty of Pharmacy, Federal University of Goiás, Goiânia, Brazil., Freitas VAQ; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil., Zara ALSA; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil., Costa CR; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil., Neves BJ; Laboratory of Cheminformatics (LabChem), Faculty of Pharmacy, Federal University of Goiás, Goiânia, Brazil., Silva MDRR; Institute of Tropical Pathology and Public Health (IPTSP), Federal University of Goiás, Goiânia, Brazil. Electronic address: rosario@ufg.br. |
| المصدر: | Journal de mycologie medicale [J Mycol Med] 2023 May; Vol. 33 (2), pp. 101363. Date of Electronic Publication: 2023 Feb 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Masson Country of Publication: France NLM ID: 9425651 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1773-0449 (Electronic) Linking ISSN: 11565233 NLM ISO Abbreviation: J Mycol Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Paris : Masson, 1991- |
| مواضيع طبية MeSH: | Histoplasmosis*/epidemiology , AIDS-Related Opportunistic Infections*/microbiology, Humans ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Drug Repositioning ; Molecular Docking Simulation ; Histoplasma/genetics |
| مستخلص: | Background: Histoplasmosis is a systemic form of endemic mycosis to the American continent and may be lethal to people living with HIV/AIDS. The drugs available for treating histoplasmosis are limited, costly, and highly toxic. New drug development is time-consuming and costly; hence, drug repositioning is an advantageous strategy for discovering new therapeutic options. Objective: This study was conducted to identify drugs that can be repositioned for treating histoplasmosis in immunocompromised patients. Methods: Homologous proteins among Histoplasma capsulatum strains were selected and used to search for homologous targets in the DrugBank and Therapeutic Target Database. Essential genes were selected using Saccharomyces cerevisiae as a model, and functional regions of the therapeutic targets were analyzed. The antifungal activity of the selected drugs was verified, and homology modeling and molecular docking were performed to verify the interactions between the drugs with low inhibitory concentration values and their corresponding targets. Results: We selected 149 approved drugs with potential activity against histoplasmosis, among which eight were selected for evaluating their in vitro activity. For drugs with low minimum inhibitory concentration values, such as mebendazole, everolimus, butenafine, and bifonazole, molecular docking studies were performed. A chemogenomic framework revealed lanosterol 14-α-demethylase, squalene monooxygenase, serine/threonine-protein kinase mTOR, and the β-4B tubulin chain of H. capsulatum, respectively, as the protein targets of the drugs. Conclusions: Our strategy can be used to identify promising antifungal targets, and drugs with repositioning potential for treating H. capsulatum. (Copyright © 2023. Published by Elsevier Masson SAS.) |
| فهرسة مساهمة: | Keywords: Antifungal agent; Drug repositioning; Histoplasmosis |
| المشرفين على المادة: | 0 (Antifungal Agents) |
| تواريخ الأحداث: | Date Created: 20230226 Date Completed: 20230515 Latest Revision: 20230515 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.mycmed.2023.101363 |
| PMID: | 36842411 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1773-0449 |
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| DOI: | 10.1016/j.mycmed.2023.101363 |