Twelve steroidal platinum(II) complexes were synthesized by reaction of potassium tetrachloroplatinate with steroidal esters of L-methionine and L-histidine. The steroidal esters coordinated as bidentate ligands via S and N donor atoms of L-methionine and via two N donor atoms of L-histidine. Cholesterol, cholestanol, diosgenine, pregnenolone, dehydroepiandrosterone, testosterone, estrone, and estradiol were used as the steroidal compounds. The esters and complexes prepared were characterized by infrared, mass, and (1)H NMR spectroscopy and elemental analysis. Platinum complexes were tested for in vitro cytotoxicity against several cancer cell lines: T-lymphoblastic leukemia CEM, breast carcinoma MCF-7, lung carcinoma A-549, multiple myeloma RPMI 8226, and one normal cell line human fibroblast BJ.
- MeSH
- estery chemická syntéza chemie toxicita MeSH
- financování organizované MeSH
- histidin chemie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- methionin chemie MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- platina chemie MeSH
- steroidy chemie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
Three types of 5alpha-androstane and ergostane analogues of brassinolide, containing a fluorine atom in either the 3alpha or the 5alpha positions or in 3alpha and 5alpha positions, were prepared using standard operations (reaction of 3beta-alcohols with (diethylamino)sulfur trifluoride, cleavage of epoxide with HF in py or BF 3.Et 2O). The 5alpha-fluorine was found to affect chemical reactivity (e.g., electrophilic addition to the Delta (2)-double bond) as well as physical properties (e.g., NMR, chromatographic behavior) of the products. Cytotoxicity of the products was studied using human normal and cancer cell lines with 28-homocastasterone as positive control and their brassinolide type activity was established using the bean second-internode test with 24-epibrassinolide as standard. The equivalence of F and OH groups was observed in some of the active compounds. The anticancer and the brassinolide-type activity do not correlate with each other: ergostane derivatives were most active in the former test while androstane derivatives were best in the latter.
- MeSH
- antitumorózní látky farmakologie chemická syntéza chemie MeSH
- buněčné linie MeSH
- cholestanoly farmakologie chemická syntéza chemie MeSH
- financování organizované MeSH
- lidé MeSH
- molekulární struktura MeSH
- sloučeniny fluoru farmakologie chemická syntéza chemie MeSH
- steroidy heterocyklické farmakologie chemická syntéza chemie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
Brassinosteroids (BRs) are steroid plant hormones that are essential for many plant growth and developmental processes, including cell expansion, vascular differentiation and stress responses. Up to now the inhibitory effects of BRs on cell division of mammalian cells are unknown. To determine basic anticancer structure-activity relationships of natural BRs on human cells, several normal and cancer cell lines have been used. Several of the tested BRs were found to have high cytotoxic activity. Therefore, in our next series of experiments, we tested the effects of the most promising and readily available BR analogues with interesting anticancer properties, 28-homocastasterone (1) and 24-epibrassinolide (2), on the viability, proliferation, and cycling of hormone-sensitive/insensitive (MCF-7/MDA-MB-468) breast and (LNCaP/DU-145) prostate cancer cell lines to determine whether the discovered cytotoxic activity of BRs could be, at least partially, related to brassinosteroid-nuclear receptor interactions. Both BRs inhibited cell growth in a dose-dependent manner in the cancer cell lines. Flow cytometry analysis showed that BR treatment arrested MCF-7, MDA-MB-468 and LNCaP cells in G(1) phase of the cell cycle and induced apoptosis in MDA-MB-468, LNCaP, and slightly in the DU-145 cells. Our results provide the first evidence that natural BRs can inhibit the growth, at micromolar concentrations, of several human cancer cell lines without affecting the growth of normal cells. Therefore, these plant hormones are promising leads for potential anticancer drugs.
New androstane brassinosteroids with 17beta-ester groups - butyrates, heptafluorobutyrates, and laurates (4-18) - were prepared. Brassinolide activity was evaluated using both the bean second internode bioassay and the rice lamina inclination test. Brassinosteroid 16 was found to be the most active by the bean second internode bioassay. This activity in the bean second internode bioassay corresponded with the field yield, while the RLIT bioassay does not.
- MeSH
- androstany farmakologie chemická syntéza chemie MeSH
- biotest MeSH
- butyráty chemie MeSH
- cholestanoly farmakologie chemická syntéza chemie MeSH
- esterifikace MeSH
- fazol růst a vývoj účinky léků MeSH
- financování organizované MeSH
- fluorokarbony chemie MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- laurany chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- rýže (rod) růst a vývoj účinky léků MeSH
- steroidy heterocyklické farmakologie chemická syntéza chemie MeSH
