Trilobolide-steroid hybrids: Synthesis, cytotoxic and antimycobacterial activity
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
27543674
DOI
10.1016/j.steroids.2016.08.011
PII: S0039-128X(16)30107-6
Knihovny.cz E-resources
- Keywords
- Click chemistry, Cytotoxicity, SAR, Steroid receptor, Steroids, Trilobolide,
- MeSH
- Receptors, Androgen metabolism MeSH
- Anti-Bacterial Agents chemical synthesis chemistry pharmacology MeSH
- A549 Cells MeSH
- Butyrates chemistry MeSH
- Candida drug effects MeSH
- Click Chemistry MeSH
- Furans chemistry MeSH
- HCT116 Cells MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, Steroid metabolism MeSH
- Steroids chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Receptors, Androgen MeSH
- Anti-Bacterial Agents MeSH
- Butyrates MeSH
- Furans MeSH
- Receptors, Estrogen MeSH
- Receptors, Steroid MeSH
- Steroids MeSH
- trilobolide MeSH Browser
Sesquiterpene lactone trilobolide is a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, thus depleting the Ins(1,4,5)P3-sensitive intracellular calcium stores. Here, we describe a synthesis of a series of 6 trilobolide-steroids conjugates (estradiol, pregnene, dehydroepiandrosterone, and testosterone). We found that the newly synthesized Tb-based compounds possess different remarkable biological activities. Cancer cell cytotoxicity and preferential selectivity is represented in our study by a Tb-pregnene derivative. The most cytotoxic clickates of estradiol and pregnene were studied by FACS where impact on cell cycle and RNA synthesis was observed; live-cell microscopy revealed the impact on cell organelle morphology particularly endoplasmic reticulum, mitochondria and nucleus. Further, we have studied the estrogenic and androgenic properties of the clickate molecules using cell-based luciferase assays. Finally, antimycobacterial tests revealed that testosterone and estradiol derivatives potentiated the antimycobacterial activity up to IC50 of 10.6μM.
References provided by Crossref.org
BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide
