In-vitro safety and off-target profile of the anti-parasitic arylmethylaminosteroid 1o.
Animals
Antimalarials
/ pharmacology
Antiparasitic Agents
/ pharmacology
Apoptosis
Caco-2 Cells
Cell Proliferation
Cell Survival
HCT116 Cells
Humans
In Vitro Techniques
Inhibitory Concentration 50
Mitochondria
/ metabolism
Parasites
/ drug effects
Parasitic Sensitivity Tests
Patient Safety
Permeability
Plasmodium falciparum
/ drug effects
Schistosoma mansoni
/ drug effects
Schistosomiasis
Steroids
/ pharmacology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
received:
28
01
2020
accepted:
15
04
2020
entrez:
7
5
2020
pubmed:
7
5
2020
medline:
8
1
2021
Statut:
epublish
Résumé
Parasite-mediated diseases like malaria and schistosomiasis are growing health problems worldwide and novel drug candidates are urgently needed. In this study, the in-vitro safety profile of steroid compound 1o (sc1o), effective against the parasites Plasmodium falciparum and Schistosoma mansoni with an IC
Identifiants
pubmed: 32371995
doi: 10.1038/s41598-020-64382-w
pii: 10.1038/s41598-020-64382-w
pmc: PMC7200784
doi:
Substances chimiques
Antimalarials
0
Antiparasitic Agents
0
Steroids
0
arylmethylaminosteroid 1o
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7534Références
Steinmann, P., Keiser, J., Bos, R., Tanner, M. & Utzinger, J. Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6, 411–425, https://doi.org/10.1016/S1473-3099(06)70521-7 (2006).
doi: 10.1016/S1473-3099(06)70521-7
pubmed: 16790382
Anisuzzaman & Tsuji, N. Schistosomiasis and hookworm infection in humans: Disease burden, pathobiology and anthelmintic vaccines. Parasitol Int 75, 102051, https://doi.org/10.1016/j.parint.2020.102051 (2020).
doi: 10.1016/j.parint.2020.102051
pubmed: 31911156
WHO. Schistosomiasis. Fact sheet N° 115 (2015). (2015).
Sinha, S., Medhi, B. & Sehgal, R. Challenges of drug-resistant malaria. Parasite 21, 61, https://doi.org/10.1051/parasite/2014059 (2014).
doi: 10.1051/parasite/2014059
pubmed: 25402734
pmcid: 4234044
Wells, T. N., Hooft van Huijsduijnen, R. & Van Voorhis, W. C. Malaria medicines: a glass half full? Nat Rev Drug Discov 14, 424–442, https://doi.org/10.1038/nrd4573 (2015).
doi: 10.1038/nrd4573
pubmed: 26000721
Utzinger, J. & Keiser, J. Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opin Pharmacother 5, 263–285, https://doi.org/10.1517/14656566.5.2.263 (2004).
doi: 10.1517/14656566.5.2.263
pubmed: 14996624
Botros, S. S. & Bennett, J. L. Praziquantel resistance. Expert Opin Drug Discov 2, S35–40, https://doi.org/10.1517/17460441.2.S1.S35 (2007).
doi: 10.1517/17460441.2.S1.S35
pubmed: 23489031
Mader, P., Rennar, G. A., Ventura, A. M. P., Grevelding, C. G. & Schlitzer, M. Chemotherapy for Fighting Schistosomiasis: Past, Present and Future. ChemMedChem 13, 2374-2389, doi:10.1002/cmdc.201800572 (2018).
Krieg, R. et al. Arylmethylamino steroids as antiparasitic agents. Nat Commun 8, 14478, https://doi.org/10.1038/ncomms14478 (2017).
doi: 10.1038/ncomms14478
pubmed: 28211535
pmcid: 5321741
Hughes, J. P., Rees, S., Kalindjian, S. B. & Philpott, K. L. Principles of early drug discovery. Br J Pharmacol 162, 1239–1249, https://doi.org/10.1111/j.1476-5381.2010.01127.x (2011).
doi: 10.1111/j.1476-5381.2010.01127.x
pubmed: 21091654
pmcid: 3058157
Hubatsch, I., Ragnarsson, E. G. & Artursson, P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc 2, 2111–2119, https://doi.org/10.1038/nprot.2007.303 (2007).
doi: 10.1038/nprot.2007.303
pubmed: 17853866
Lynch, T. & Price, A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76, 391–396 (2007).
pubmed: 17708140
Kalyaanamoorthy, S. & Barakat, K. H. Development of Safe Drugs: The hERG Challenge. Med Res Rev 38, 525–555, https://doi.org/10.1002/med.21445 (2018).
doi: 10.1002/med.21445
pubmed: 28467598
Porter, A. G. & Janicke, R. U. Emerging roles of caspase-3 in apoptosis. Cell death and differentiation 6, 99–104, https://doi.org/10.1038/sj.cdd.4400476 (1999).
doi: 10.1038/sj.cdd.4400476
pubmed: 10200555
Moraes, C. B. et al. Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform. SLAS Discov 24, 346–361, https://doi.org/10.1177/2472555218823171 (2019).
doi: 10.1177/2472555218823171
pubmed: 30784368
pmcid: 6484532
Rothen-Rutishauser, B., Riesen, F. K., Braun, A., Gunthert, M. & Wunderli-Allenspach, H. Dynamics of tight and adherens junctions under EGTA treatment. J Membr Biol 188, 151–162, https://doi.org/10.1007/s00232-001-0182-2 (2002).
doi: 10.1007/s00232-001-0182-2
pubmed: 12172640
Sharma, P., Varma, M. V., Chawla, H. P. & Panchagnula, R. Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers. Farmaco 60, 884–893, https://doi.org/10.1016/j.farmac.2005.08.008 (2005).
doi: 10.1016/j.farmac.2005.08.008
pubmed: 16226752
pmcid: 16226752
Paudwal, G. et al. Recent Advances in Solid Dispersion Technology for Efficient Delivery of Poorly Water-Soluble Drugs. Curr Pharm Des 25, 1524–1535, https://doi.org/10.2174/1381612825666190618121553 (2019).
doi: 10.2174/1381612825666190618121553
pubmed: 31258070