Author | Sass, Gabriele | |
Author | Tsamo, Armelle T | |
Author | Chounda, Gwladys A M | |
Author | Nangmo, Pamela K | |
Author | Sayed, Nazish | |
Author | Bozzi, Adriana | |
Author | Wu, Joseph C | |
Author | Nkengfack, Augustin E | |
Author | Stevens, David A | |
Access date | 2023-05-12T17:55:37Z | |
Available date | 2023-05-12T17:55:37Z | |
Document date | 2019 | |
Citation | SASS, Gabriele et al. Vismione B Interferes with Trypanosoma cruzi Infection of Vero Cells and Human Stem Cell-Derived Cardiomyocytes. Am J Trop Med Hyg., v. 101, n. 6, p. 1359-1368, 2019. doi: 10.4269/ajtmh.19-0350. | en_US |
ISSN | 0002-9637 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/58366 | |
Sponsorship | NATIONAL INSTITUTES OF HEALTH | en_US |
Language | eng | en_US |
Publisher | American Society of Tropical Medicine and Hygiene | en_US |
Rights | restricted access | |
Title | Vismione B Interferes with Trypanosoma cruzi Infection of Vero Cells and Human Stem Cell-Derived Cardiomyocytes | en_US |
Type | Article | |
DOI | 10.4269/ajtmh.19-0350 | |
Abstract | Traditional African medicine is a source of new molecules that might be useful in modern therapeutics. We tested ten limonoids, six quinones, one xanthone, one alkaloid, and one cycloartane, isolated from four Cameroonian medicinal plants, and one plant-associated endophytic fungus, against Trypanosoma cruzi, the etiological agent of Chagas disease (CD). Vero cells, or human-induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (hiPSC-CM) were infected with T. cruzi trypomastigotes (discrete typing unit types I or II). Infection took place in the presence of drugs, or 24 hours before drug treatment. Forty-eight hours after infection, infection rates and parasite multiplication were evaluated by Giemsa stain. Cell metabolism was measured to determine functional integrity. In Vero cells, several individual molecules significantly affected T. cruzi infection and multiplication with no, or minor, effects on cell viability. Reduced infection rates and multiplication by the quinone vismione B was superior to the commonly used therapeutic benznidazole (BNZ). The vismione B concentration inhibiting 50% of T. cruzi infection (IC50) was 1.3 mu M. When drug was applied after infection, anti-Trypanosoma effects of vismione B [10 mu M) were significantly stronger than effects of BNZ (23 mu M). Furthermore, in hiPSC-CM cultures, infection and multiplication rates in the presence of vismione B (10 mu M) were significantly lower than in BNZ (11.5 mu M), without showing signs of cytotoxicity. Our data indicate that vismione B is more potent against T. cruzi infection and multiplication than BNZ, with stronger effects on established infection. Vismione B, therefore, might become a promising lead molecule for treatment development for CD. | en_US |
Affilliation | California Institute for Medical Research. San Jose, California. | en_US |
Affilliation | Department of Organic Chemistry. Faculty of Science. University of Yaoundé I. Yaoundé, Cameroon. | en_US |
Affilliation | Department of Organic Chemistry. Faculty of Science. University of Yaoundé I. Yaoundé, Cameroon. | en_US |
Affilliation | Department of Organic Chemistry. Faculty of Science. University of Yaoundé I. Yaoundé, Cameroon. | en_US |
Affilliation | Department of Radiology. School of Medicine. Stanford University. Stanford, California/Division of Cardiology. Department of Medicine. School of Medicine. Stanford University. Stanford, California/Institute of Stem Cell Biology and Regenerative Medicine. School of Medicine. Stanford University. Stanford, California/Department of Medicine. School of Medicine. Stanford University. Stanford, California. | en_US |
Affilliation | California Institute for Medical Research. San Jose, California/Department of Radiology. School of Medicine. Stanford University. Stanford, California/Division of Cardiology. Department of Medicine. School of Medicine. Stanford University. Stanford, California/Institute of Stem Cell Biology and Regenerative Medicine. School of Medicine. Stanford University. Stanford, California/Department of Medicine. School of Medicine. Stanford University. Stanford, California/Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Radiology. School of Medicine. Stanford University. Stanford, California/Division of Cardiology. Department of Medicine. School of Medicine. Stanford University. Stanford, California/Institute of Stem Cell Biology and Regenerative Medicine. School of Medicine. Stanford University. Stanford, California/Department of Medicine. School of Medicine. Stanford University. Stanford, California. | en_US |
Affilliation | Department of Organic Chemistry. Faculty of Science. University of Yaoundé I. Yaoundé, Cameroon. | en_US |
Affilliation | California Institute for Medical Research. San Jose, California/Institute René Rachou. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |