Tamoxifen-based compounds in the breast cancer therapy
2022
Authors:
Kazimir, AleksandrSchwarze, Benedikt
Jelača, Sanja
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Hey-Hawkins, Evamarie
Document Type:
Conference object (Published version)
,
© 2022 by the Society of Biological Inorganic Chemistry
Metadata
Show full item recordAbstract:
Tamoxifen (Scheme 1, 1) is historically well known for its successful application in the therapy of
the oestrogen receptor positive (ERα+) breast cancer.1
In this study, we combine a tamoxifenbased ligand2
(Scheme 1, 3) with transition metal complex moieties of platinum(II), palladium(II),
copper(II), and nickel(II)3
containing chlorides (Scheme 1, 4-6) or a bulky, hydrophobic and stable
nido-dicarborate ligand (Scheme 1, 7-9). We investigated the anticancer activity of the
compounds 2-9 in in vitro cell assays. The incorporation of a 2,2’-bipyridine unit into a tamoxifen-inspired structure 3 increases the
cytotoxic activity compared to compound 2 against several cell lines including ERα+ human
glioblastoma (U251), breast adenocarcinoma (MCF-7, MDA-MB-361) and triple negative (ERα−)
MDA-MB-231. The formation of PtII and PdII chloride complexes (4 and 5) insignificantly improve
the activity compared to ligand 3. The ability of the CuII chloride moiety for ligand exchange in
solution explains the significant rise of the cytotoxicity of 6 compared to 4 and 5. However, the
incorporation of a nido-carborate dianion into Pt and Ni complexes (7 and 9) neutralised on
average their toxicity towards all studied cell lines, except compound 8 which was active against
U251 and MDA-MB-231. The observed cytotoxicity data of compounds 3-6 and 8 against MDAMB-231 (ERα−) suggest other off-target mechanisms rather than only ERα inhibition which is
usual for metallodrugs.
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- 16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France. Society of Biological Inorganic Chemistry; 2022. BI31.