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Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives
- Source :
- European Journal of Medicinal Chemistry. 54:784-792
- Publication Year :
- 2012
-
Abstract
- New 17-picolyl and 17-picolinylidene androstane derivatives, 3 – 10 , 15 , 18 , 19 , 22 and 23 , were synthesized starting from 17α-picolyl-androst-5-en-3β,17β-diol ( 1 ) and 17(Z)-picolinylidene-androst-5-en-3β-ol ( 2 ). Reaction of 1 with m -chloroperoxybenzoic acid gives 5α,6α-epoxy N-oxide derivative 3 , or, with Jones reagent, 3,6-dione derivative 4 ; while 17α-picolyl-androst-5-en-3β,4α,17β-triol ( 5 ) or 3β,4β,17β-triol ( 6 ) derivatives are obtainable from 1 using SeO 2 in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10 . Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12 , which, with H 2 O 2 in 4 M NaOH, affords 4α,5α and 4β,5β-epoxides 13 , 14 , 16 and 17 . New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14 , or, with methanol in 4 M NaOH, from 16 and 17 . Reduction of 11 with NaBH 4 gives 22, which was then acetylated to obtain 23 . All new derivatives were screened for antitumor activity against human breast adenocarcinoma ER+, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3 , 5 , 6 , 8 , 10 , 18 , 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5 , 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells.
- Subjects :
- Pharmacology
biology
Stereochemistry
Organic Chemistry
Oppenauer oxidation
Antineoplastic Agents
Chemistry Techniques, Synthetic
General Medicine
Conjugated system
medicine.disease
biology.organism_classification
HeLa
Inhibitory Concentration 50
chemistry.chemical_compound
chemistry
Tosyl
Cell Line, Tumor
Reagent
Drug Discovery
medicine
Humans
Adenocarcinoma
Androstane
Cytotoxicity
Androstanes
Subjects
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....0b11b4852610524bd7cac7344b8e552f
- Full Text :
- https://doi.org/10.1016/j.ejmech.2012.06.030