Next Article in Journal
A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development
Previous Article in Journal
Ethosomes and Transethosomes as Cutaneous Delivery Systems for Quercetin: A Preliminary Study on Melanoma Cells
Previous Article in Special Issue
LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection
 
 
Article

Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

1
Department of Clinical Analysis, School of Pharmaceutical Science, Universidade Estadual Paulista, Araraquara 14800-903, SP, Brazil
2
Department of Scienze di Base e Applicate per l’Ingegneria, Sapienza University of Rome, Via Castro Laurenziano 7, 00185 Rome, Italy
3
Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
4
Department of Chimica e Tecnologia del Farmaco, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
5
Department of Chemistry and Technology of Drug, Istituto Pasteur, Fondazione Cenci Bolognetti, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Clive Prestidge
Pharmaceutics 2022, 14(5), 1043; https://doi.org/10.3390/pharmaceutics14051043
Received: 7 April 2022 / Revised: 4 May 2022 / Accepted: 9 May 2022 / Published: 12 May 2022
(This article belongs to the Special Issue Recent Advances in Antifungal Drugs)
Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with a minimum inhibitory concentration (MIC90) equal to or lower than 7.81 µg/mL were selected to evaluate their MIC90 on ATCC G217-B strain and their minimum fungicide concentration (MFC) on both strains. The quantification of membrane ergosterol, cell wall integrity, the production of reactive oxygen species, and the induction of death by necrosis–apoptosis was performed to investigate the mechanism of action of compounds 7, 11, and 32. These compounds could reduce the extracted sterol and induce necrotic cell death, similarly to itraconazole. Moreover, 7 and 11 damaged the cell wall, causing flaws in the contour (11), or changing the size and shape of the fungal cell wall (7). Furthermore, 7 and 32 induced reactive oxygen species (ROS) formation higher than 11 and control. Finally, the cytotoxicity was measured in two models of cell culture, i.e., monolayers (cells are flat) and a three-dimensional (3D) model, where they present a spheroidal conformation. Cytotoxicity assays in the 3D model showed a lower toxicity in the compounds than those performed on cell monolayers. Overall, these results suggest that derivatives of nitrofurans and indoles are promising compounds for the treatment of histoplasmosis. View Full-Text
Keywords: Histoplasma capsulatum; three-dimensional models; nitrofurans; indoles; pharmacological replacement; mechanisms of action; cytotoxicity; antifungal activity; drug repositioning; spheroids Histoplasma capsulatum; three-dimensional models; nitrofurans; indoles; pharmacological replacement; mechanisms of action; cytotoxicity; antifungal activity; drug repositioning; spheroids
Show Figures

Figure 1

MDPI and ACS Style

Vaso, C.O.; Bila, N.M.; Pandolfi, F.; De Vita, D.; Bortolami, M.; Bonatti, J.L.C.; De Moraes Silva, R.A.; Gonçalves, L.N.C.; Tudino, V.; Costi, R.; Di Santo, R.; Mendes-Giannini, M.J.S.; Costa-Orlandi, C.B.; Scipione, L.; Fusco-Almeida, A.M. Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures. Pharmaceutics 2022, 14, 1043. https://doi.org/10.3390/pharmaceutics14051043

AMA Style

Vaso CO, Bila NM, Pandolfi F, De Vita D, Bortolami M, Bonatti JLC, De Moraes Silva RA, Gonçalves LNC, Tudino V, Costi R, Di Santo R, Mendes-Giannini MJS, Costa-Orlandi CB, Scipione L, Fusco-Almeida AM. Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures. Pharmaceutics. 2022; 14(5):1043. https://doi.org/10.3390/pharmaceutics14051043

Chicago/Turabian Style

Vaso, Carolina Orlando, Níura Madalena Bila, Fabiana Pandolfi, Daniela De Vita, Martina Bortolami, Jean Lucas Carvalho Bonatti, Rosângela Aparecida De Moraes Silva, Larissa Naiara Carvalho Gonçalves, Valeria Tudino, Roberta Costi, Roberto Di Santo, Maria José Soares Mendes-Giannini, Caroline Barcelos Costa-Orlandi, Luigi Scipione, and Ana Marisa Fusco-Almeida. 2022. "Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures" Pharmaceutics 14, no. 5: 1043. https://doi.org/10.3390/pharmaceutics14051043

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop