New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies.
Cell Cycle
/ drug effects
Cell Death
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
DNA
/ metabolism
Estrogen Receptor alpha
/ metabolism
Estrogens
/ pharmacology
Estrone
/ chemical synthesis
Fluorouracil
/ pharmacology
Humans
Inhibitory Concentration 50
Molecular Docking Simulation
Oximes
/ chemical synthesis
cancer
cytotoxicity
docking
estrone
oximes
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
04 May 2021
04 May 2021
Historique:
received:
25
03
2021
revised:
28
04
2021
accepted:
01
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
25
6
2021
Statut:
epublish
Résumé
The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ
Identifiants
pubmed: 34064380
pii: molecules26092687
doi: 10.3390/molecules26092687
pmc: PMC8125528
pii:
doi:
Substances chimiques
Estrogen Receptor alpha
0
Estrogens
0
Oximes
0
estrone oxime
0
Estrone
2DI9HA706A
DNA
9007-49-2
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation
ID : Project POCI-01-0145-FEDER-007491
Organisme : FCT - Foundation for Science and Technology
ID : Project UID/Multi /00709/2013
Références
Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003
pubmed: 9600906
Org Med Chem Lett. 2011 Oct 04;1(1):12
pubmed: 22373136
J Med Chem. 1995 Jun 9;38(12):2041-9
pubmed: 7783135
Bioorg Med Chem. 2017 Apr 1;25(7):2065-2073
pubmed: 28254377
Endocr Relat Cancer. 2008 Sep;15(3):665-92
pubmed: 18541621
J Steroid Biochem Mol Biol. 2015 Jun;150:123-34
pubmed: 25845933
Sci Rep. 2018 Mar 9;8(1):4242
pubmed: 29523799
J Med Chem. 2005 Sep 8;48(18):5749-70
pubmed: 16134943
J Biomol Struct Dyn. 2015 Sep;33(9):2048-58
pubmed: 25407587
Steroids. 2010 Dec;75(12):825-33
pubmed: 20685325
Arch Pharm (Weinheim). 2001 Apr;334(4):138-40
pubmed: 11382149
Endocr Rev. 2004 Dec;25(6):947-70
pubmed: 15583024
Clin Cancer Res. 2002 Nov;8(11):3311-4
pubmed: 12429616
Molecules. 2011 Nov 28;16(12):9868-85
pubmed: 22124202
J Biol Chem. 2003 Jun 20;278(25):22989-97
pubmed: 12657638
J Biomol Screen. 2012 Aug;17(7):921-32
pubmed: 22498909
Cancer Res. 1993 Oct 1;53(19):4573-81
pubmed: 8402630
Cancer Lett. 2005 Sep 28;227(2):115-24
pubmed: 16112414
Int J Mol Sci. 2017 Aug 09;18(8):
pubmed: 28792473
Steroids. 1976 Nov;28(5):733
pubmed: 1014044
J Steroid Biochem Mol Biol. 2005 Feb;94(1-3):239-51
pubmed: 15862971
Int J Mol Sci. 2015 Jan 28;16(2):2942-55
pubmed: 25636036
J Med Chem. 1997 Jul 18;40(15):2323-34
pubmed: 9240348
J Med Chem. 2001 Aug 2;44(16):2612-8
pubmed: 11472215
Steroids. 2013 Jan;78(1):69-78
pubmed: 23127813
J Steroid Biochem Mol Biol. 1994 Jul;50(1-2):75-84
pubmed: 8049136
J Med Chem. 2000 Nov 2;43(22):4266-77
pubmed: 11063622
Molecules. 2011 Dec 30;17(1):355-68
pubmed: 22210173
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
Molecules. 2009 Nov 17;14(11):4655-68
pubmed: 19924093
Curr Med Chem. 2018 Feb 21;25(6):660-686
pubmed: 28971759
Steroids. 2016 Jun;110:9-34
pubmed: 27020471
Mol Endocrinol. 2010 Apr;24(4):832-45
pubmed: 20172961
Steroids. 2011 Dec 20;76(14):1554-9
pubmed: 21964577
Front Oncol. 2014 Jun 18;4:153
pubmed: 24995158
Molecules. 2018 Nov 12;23(11):
pubmed: 30424582
Mol Cancer Ther. 2012 Oct;11(10):2096-104
pubmed: 22914440
Acta Pharm Sin B. 2017 Mar;7(2):119-136
pubmed: 28303218
Eur J Med Chem. 2017 Oct 20;139:390-400
pubmed: 28810190
Molecules. 2016 Nov 14;21(11):
pubmed: 27854258
Curr Comput Aided Drug Des. 2011 Jun;7(2):146-57
pubmed: 21534921
J Med Chem. 2006 Feb 23;49(4):1325-45
pubmed: 16480268
Nature. 2004 Mar 11;428(6979):198-202
pubmed: 15014504
Steroids. 1995 Dec;60(12):809-11
pubmed: 8650703
Drug Discov Today. 2003 Sep 1;8(17):793-802
pubmed: 12946642
Exp Cell Res. 2007 Oct 1;313(16):3635-44
pubmed: 17643424
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13775-9
pubmed: 19666559
Chem Biol Drug Des. 2019 Sep;94(3):1584-1595
pubmed: 31148379
J Med Chem. 1999 Aug 12;42(16):3188-92
pubmed: 10447965
Int J Mol Sci. 2019 May 02;20(9):
pubmed: 31052551