Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells
- PMID: 8350087
- DOI: 10.1021/np50096a007
Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells
Abstract
A series of artemisinin-related endoperoxides was tested for cytotoxicity to Ehrlich ascites tumor (EAT) cells using the microculture tetrazolium (MTT) assay. Artemisinin [1] had an IC50 value of 29.8 microM. Derivatives of dihydroartemisinin [2], being developed as antimalarial drugs (artemether [3], arteether [4], sodium artesunate [5], artelinic acid [6], and sodium artelinate [7]), exhibited a somewhat more potent cytotoxicity. Their IC50 values ranged from 12.2 to 19.9 microM. The presence of an exocyclic methylene fused to the lactone ring, as for artemisitene [9], led to higher cytotoxicity than 1. From the two epimeric 11-hydroxyartemisinin derivatives, the R form 12 showed a considerably higher cytotoxicity than the S form 13. Opening of the lactone ring of 1 dramatically reduced the cytotoxicity. The ether dimer 8 of 2 was the most potent cytotoxic agent, its IC50 being 1.4 microM. The variations in cytotoxicity between the structurally related compounds mostly correlated well with the theoretical capacity of radical formation and stabilization. In some cases lipophilicity or the presence of an electrophilic moiety seemed to have a determinant influence on cytotoxicity. The artemisinin-related endoperoxides showed cytotoxicity to EAT cells at higher concentrations than those needed for in vitro antimalarial activity, as reported in the literature.
Similar articles
-
Stereochemistry-dependent cytotoxicity of some artemisinin derivatives.J Nat Prod. 1997 Apr;60(4):325-30. doi: 10.1021/np9605495. J Nat Prod. 1997. PMID: 9134741
-
Stability of artemisinin in aqueous environments: impact on its cytotoxic action to Ehrlich ascites tumour cells.J Pharm Pharmacol. 1997 Dec;49(12):1254-8. doi: 10.1111/j.2042-7158.1997.tb06080.x. J Pharm Pharmacol. 1997. PMID: 9466353
-
Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells.Planta Med. 1998 Oct;64(7):615-9. doi: 10.1055/s-2006-957533. Planta Med. 1998. PMID: 9810267
-
Considerations on the mechanism of action of artemisinin antimalarials: part 1--the 'carbon radical' and 'heme' hypotheses.Infect Disord Drug Targets. 2013 Aug;13(4):217-77. doi: 10.2174/1871526513666131129155708. Infect Disord Drug Targets. 2013. PMID: 24304352 Review.
-
Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy.Microbiol Rev. 1996 Jun;60(2):301-15. doi: 10.1128/mr.60.2.301-315.1996. Microbiol Rev. 1996. PMID: 8801435 Free PMC article. Review.
Cited by
-
Biological evaluation of novel side chain containing CQTrICh-analogs as antimalarials and their development as PfCDPK1 kinase inhibitors.Heliyon. 2024 Jan 23;10(3):e25077. doi: 10.1016/j.heliyon.2024.e25077. eCollection 2024 Feb 15. Heliyon. 2024. PMID: 38327451 Free PMC article.
-
In vitro and in vivo antiplasmodial evaluation of sugar-modified nucleoside analogues.Sci Rep. 2023 Jul 28;13(1):12228. doi: 10.1038/s41598-023-39541-4. Sci Rep. 2023. PMID: 37507429 Free PMC article.
-
Artemisitene: a promising natural drug candidate with various biological activities needs to confirm the interactional targets.Front Pharmacol. 2023 Jun 15;14:1221291. doi: 10.3389/fphar.2023.1221291. eCollection 2023. Front Pharmacol. 2023. PMID: 37397487 Free PMC article. No abstract available.
-
Anti-proliferative activity of Artemisia marschalliana on cancerous cell lines.BMC Complement Med Ther. 2023 Apr 14;23(1):119. doi: 10.1186/s12906-023-03887-z. BMC Complement Med Ther. 2023. PMID: 37059982 Free PMC article.
-
Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels.J Gastrointest Oncol. 2022 Oct;13(5):2144-2153. doi: 10.21037/jgo-22-877. J Gastrointest Oncol. 2022. PMID: 36388666 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources