219843-75-1Relevant articles and documents
Synthesis, Characterization, and Biological Properties of Steroidal Ruthenium(II) and Iridium(III) Complexes Based on the Androst-16-en-3-ol Framework
Koch, Vanessa,Meschkov, Anna,Feuerstein, Wolfram,Pfeifer, Juliana,Fuhr, Olaf,Nieger, Martin,Schepers, Ute,Br?se, Stefan
, p. 15917 - 15926 (2019/11/21)
A range of novel cyclometalated ruthenium(II) and iridium(III) complexes with a steroidal backbone based on androsterone were synthesized and characterized by NMR spectroscopy and X-ray crystallography. Their cytotoxic properties in RT112 and RT112 cP (cisplatin-resistant) cell lines as well as in MCF7 and somatic fibroblasts were compared with those of the corresponding nonsteroidal complexes and the noncyclometalated pyridyl complexes as well as with cisplatin as reference. All steroidal complexes were more active in RT112 cP cells than cisplatin, whereby the cyclometalated pyridinylphenyl complexes based on 5c showed high cytotoxicity while maintaining low resistant factors of 0.33 and 0.50.
Stille and Suzuki Cross-Coupling Reactions as Versatile Tools for Modifications at C-17 of Steroidal Skeletons – A Comprehensive Study
Koch, Vanessa,Nieger, Martin,Br?se, Stefan
, p. 832 - 840 (2017/03/11)
Herein, we report on a comparative Stille and Suzuki cross-coupling study of steroidal vinyl (pseudo)halides with different boronic acids and tributyltin organyls. Furthermore, we have investigated the “inverse” case of those cross-coupling reactions, i.e., the reaction of a steroidal vinylpinacolatoborane or a tributyltin steroid with various bromides. The development of both methods allows the introduction of different residues at C-17 of steroid skeletons providing access to a broad variety of steroid analogues which are of high interest for biological screenings or natural product synthesis. (Figure presented.).
The 16,17-double bond is needed for irreversible inhibition of human cytochrome P45017α by abiraterone (17-(3-pyridyl)androsta-5,16-dien-3β- ol) and related steroidal inhibitors
Jarman,Barrie,Llera
, p. 5375 - 5381 (2007/10/03)
Abiraterone (17-(3-pyridyl)androsta-5,16-dien-3β-ol, 1) is a potent inhibitor (IC50 4 nM for hydroxylase) of human cytochrome P45017α. To assist in studies of the role of the 16,17-double bond in its mechanism of action, the novel 17α-(4-pyridyl)androst-5-en-3β-ol (5) and 17β-(3- pyridyl)-16,17α-epoxy-5α-androst-3β-ol (6) were synthesized. 3β- Acetoxyetienic acid was converted in three steps into 5 via photolysis of the thiohydroxamic ester 8. Oxidation of an appropriate 16,17-unsaturated precursor (21) with CrO3-pyridine afforded the acetate (23) of 6. Inhibition of the enzyme by 1, the similarly potent 5,6-reduced analogue 19 (IC50 5 nM), and the 4,16-dien-3-one 26 (IC50 3 nM) and by the less potent (IC50 13 nM) 3,5,16-triene 25 is slow to occur but is enhanced by preincubation of the inhibitor with the enzyme. Inhibition following preincubation with these compounds is not lessened by dialysis for 24 h, implying irreversible binding to the enzyme. In contrast under these conditions the still potent (IC50 27 nM) 17α-(4-pyridyl)androst-5-en-3β-ol (5) showed partial reversal after 5 h of dialysis and complete reversal of inhibition after 24 h. This behavior was also shown by the less potent 16,17-reduced 3-pyridyl compounds 3 and 24. Further, in contrast to the compounds (1, 19, 25, 26) with the 16,17-double bond, the inhibition of the enzymic reaction was not enhanced by preincubation either with 5 or with the 17β-pyridyl analogues 3, 4, and 24 which also lack this structural feature. The results show that the 16,17- double bond is necessary for irreversible binding of these pyridyl steroids to cytochrome P45017α. However oxidation to an epoxide is probably not involved since epoxide 6 was only a moderately potent inhibitor (IC50 260 nM).
