Synthesis and evaluation of Na+/K+-ATP-ase inhibiting and cytotoxic in vitro activities of oleandrigenin and its selected 17β-(butenolidyl)- and 17β-(3-furyl)- analogues
Language English Country France Media print-electronic
Document type Journal Article
PubMed
32645647
DOI
10.1016/j.ejmech.2020.112520
PII: S0223-5234(20)30492-X
Knihovny.cz E-resources
- Keywords
- ATP-ase inhibition, Apoptosis, Cardenolides, Cytotoxicity, Furan transformation, Partial synthesis,
- MeSH
- Apoptosis drug effects MeSH
- Cell Line MeSH
- Cell Cycle drug effects MeSH
- Enzyme Inhibitors chemical synthesis chemistry pharmacology MeSH
- Cardenolides chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Molecular Conformation MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Sodium-Potassium-Exchanging ATPase antagonists & inhibitors metabolism MeSH
- Stereoisomerism MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Enzyme Inhibitors MeSH
- Cardenolides MeSH
- oleandrigenin MeSH Browser
- Antineoplastic Agents MeSH
- Sodium-Potassium-Exchanging ATPase MeSH
Natural cardiac-active principles built upon the 14,16β-dihydroxy-5β,14β-androstane core and bearing a heterocyclic substituent at 17β, in particular, a cardenolide - oleandrin and a bufadienolide - bufotalin, are receiving a great deal of attention as potential anticancer drugs. The densely substituted and sterically shielded ring D is the particular structural feature of these compounds. The first synthesis of oleandrigenin from easily available steroid starting material is reported here. Furthermore, selected 17β-(4-butenolidyl)- and 17β-(3-furyl)-14,16β-dihydroxy-androstane derivatives were en route synthesized and examined for their Na+/K+-ATP-ase inhibitory properties as well as cytotoxic activities in normal and cancer cell lines. It was found that the furyl-analogue of oleandrigenin/bufatalin (7) and some related 17-(3-furyl)- derivatives (19, 21) show remarkably high Na+/K+-ATP-ase inhibitory activity as well as significant cytotoxicity in vitro. In addition, oleandrigenin 2 compared to derivatives 21 and 25 induced strong apoptosis in human cervical carcinoma HeLa cells after 24 h of treatment.
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