In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis.
DNA damage
Echinococcus granulosus sensu stricto
cystic echinococcosis
harmine derivatives
β-carboline
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2023
2023
Historique:
received:
27
04
2023
accepted:
08
08
2023
medline:
29
8
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
epublish
Résumé
Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 μM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.
Identifiants
pubmed: 37637266
doi: 10.2147/DDDT.S419002
pii: 419002
pmc: PMC10454840
doi:
Substances chimiques
Harmine
4FHH5G48T7
Antiparasitic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2441-2454Informations de copyright
© 2023 Chen et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
Pharmacol Res. 2006 Aug;54(2):150-7
pubmed: 16750635
PLoS Negl Trop Dis. 2017 Feb 9;11(2):e0005370
pubmed: 28182659
Infect Dis Poverty. 2016 Feb 19;5:13
pubmed: 26895758
Fundam Clin Pharmacol. 2003 Apr;17(2):205-12
pubmed: 12667231
Oncotarget. 2015 Apr 20;6(11):8988-9001
pubmed: 25940702
J Vet Med Sci. 2022 Mar 30;84(3):465-472
pubmed: 35125374
Environ Mol Mutagen. 2000;35(3):206-21
pubmed: 10737956
Eur J Med Chem. 2015 Apr 13;94:45-55
pubmed: 25747498
J Nat Prod. 2016 Mar 25;79(3):629-61
pubmed: 26852623
Molecules. 2020 Sep 23;25(19):
pubmed: 32977642
Dis Markers. 2020 Jul 1;2020:8259820
pubmed: 32714467
Eur J Med Chem. 2021 Nov 15;224:113687
pubmed: 34274829
Pestic Biochem Physiol. 2019 Mar;155:26-35
pubmed: 30857624
Eur J Med Chem. 2018 Dec 5;160:23-36
pubmed: 30317023
J Antimicrob Chemother. 2017 Nov 01;72(11):3122-3130
pubmed: 28981899
Exp Parasitol. 2021 Jul-Aug;226-227:108121
pubmed: 34097889
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Jul;245:109038
pubmed: 33794375
Antimicrob Agents Chemother. 2012 Aug;56(8):4207-13
pubmed: 22615284
J Biomed Nanotechnol. 2020 Jun 1;16(6):827-841
pubmed: 33187579
J Clin Microbiol. 2016 Mar;54(3):518-23
pubmed: 26677245
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):258-267
pubmed: 28625859
J Med Chem. 2012 Jul 26;55(14):6489-501
pubmed: 22770529
Arch Pharm Res. 2020 Dec;43(12):1259-1275
pubmed: 33206346
Front Cell Infect Microbiol. 2021 Nov 11;11:747739
pubmed: 34858873
Eur J Med Chem. 2020 Feb 1;187:111927
pubmed: 31812035
Biochem Biophys Res Commun. 1984 Aug 30;123(1):291-8
pubmed: 6477583
J Parasitol. 2017 Dec;103(6):699-707
pubmed: 28902565
Pharmacogn Rev. 2013 Jul;7(14):199-212
pubmed: 24347928
Clin Microbiol Rev. 2019 Feb 13;32(2):
pubmed: 30760475
Sci Rep. 2016 Sep 14;6:33204
pubmed: 27625151
Molecules. 2020 Jan 16;25(2):
pubmed: 31963275
Life (Basel). 2022 May 02;12(5):
pubmed: 35629345
Am J Transl Res. 2020 May 15;12(5):1658-1671
pubmed: 32509167
Pharmacol Ther. 2020 Dec;216:107658
pubmed: 32777330
Exp Parasitol. 2005 May;110(1):88-90
pubmed: 15804383