New cholic acid analogs: synthesis and 17β-hydroxydehydrogenase (17β-HSD) inhibition activity
-
Najim A. Al-Masoudi
,
Abbas Sami
Abstract
The 17β-hydroxysteroid dehydrogenase (17β-HSD) enzyme family is involved in the biosynthesis of active steroids and its inhibition constitutes an interesting approach for treating estrogen-, androgen-dependent cancers and osteoporosis. In this study, a new series of cholic acid analogs was designed with the goal of improving the biological activity as 17β-HSD1 and 17β-HSD2 inhibitors. To this end, 23-cholyl amides 4–7, 3-O-p-toluenesulfonyl-23-cholyl amides 10–12, 23-cholyl-carbohydrazide 14, carbothioamide analog 15, and 23-cholyl-acylhydrazone derivatives 18–22 were synthesized from cholic acid (3) via coupling, sulfonation and substitution reactions. Basic treatment of keto group of 5 with p-bromoaniline afforded 8, meanwhile acidic treatment of 3 with thiosemicarbazide furnished the 23-cholyl-thiadiazole derivative 16. The synthesized compounds were evaluated for their inhibition activity against 17β-HSD1 and 17β-HSD2, and were found inactive at 1.0 μm concentration (inhibition <10%). However, the steroids 12, 21 and 22 showed inhibition of 21.1, 23.9 and 21.3%, respectively, against 17β-HSD2 at the same concentration. Therefore, these steroidal analogs can be further structurally modified to optimize their inhibition activity against 17β-HSD2 for the development of potential therapeutics.
Acknowledgment
We thank Miss A. Friemel of the Department of Chemistry, University of Konstanz, Germany, for the 2D-NMR experiments.
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Articles in the same Issue
- Frontmatter
- In this Issue
- Does Lewis basicity correlate with catalytic performance in zerovalent group 8 complexes?
- Crystal structure and luminescence properties of a new dinuclear bismuth(III) coordination polymer containing three types of ligands
- Syntheses, structures, and catalytic properties of two arene-ruthenium(II) complexes bearing N-(2-pyridinyl)aminodiphenylphosphine sulfide ligands
- Synthesis, characterization, anticancer and antimicrobial study of arene ruthenium(II) complexes with 1,2,4-triazole ligands containing an α-diimine moiety
- Green synthesis of α-aminophosphonates using ZnO nanoparticles as an efficient catalyst
- Nano-NiZr4(PO4)6 as a superior catalyst for the synthesis of propargylamines under ultrasound irradiation
- Efficient pseudo five-component synthesis of 4,4′-(arylmethylene)-bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives promoted by a novel ionic liquid catalyst
- Hydrothermal synthesis and crystal structure of a bisupporting Keggin-polyoxometalate hybrid compound decorated with a copper(II) complex unit
- Synthesis, crystal structure, luminescence and electrochemical properties of a Salamo-type trinuclear cobalt(II) complex
- New cholic acid analogs: synthesis and 17β-hydroxydehydrogenase (17β-HSD) inhibition activity
- Synthesis, vibrational spectra and single-crystal structure determination of lithium tricyanomethanide Li[C(CN)3]
- Silber(I)-cyanid-Komplexe mit Aminen und Azaaromaten
- The alkaline earth-palladium-germanides Sr3Pd4Ge4 and BaPdGe
- Equiatomic rare earth rhodium plumbides RERhPb (RE=Y, La–Nd, Sm, Gd–Lu) with ZrNiAl-type structure
- Notes
- Synthesis and crystal structure of [azido-bis(cis-1,2-diaminocyclohexane)copper(II)] chloride trihydrate
- A Co(II) complex from a pyridylamide ligand: synthesis and structural characterization
