Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines

Ivana Predarska; Mohamad Saoud; Ibrahim Morgan; Peter Lönnecke; Goran N Kaluđerović; Evamarie Hey-Hawkins

doi:10.3390/biom13040595

Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines

Biomolecules. 2023 Mar 26;13(4):595. doi: 10.3390/biom13040595.

Authors

Ivana Predarska^{1

2}, Mohamad Saoud³, Ibrahim Morgan³, Peter Lönnecke¹, Goran N Kaluđerović^{2

3}, Evamarie Hey-Hawkins¹

Affiliations

¹ Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, Leipzig University, Johannisallee 29, 04103 Leipzig, Germany.
² Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard Leibnitz-Str. 2, 06217 Merseburg, Germany.
³ Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany.

Abstract

Organotin(IV) carboxylates are a class of compounds explored as alternatives to platinum-containing chemotherapeutics due to propitious in vitro and in vivo results, and distinct mechanisms of action. In this study, triphenyltin(IV) derivatives of non-steroidal anti-inflammatory drugs (indomethacin (HIND) and flurbiprofen (HFBP)) are synthesized and characterized, namely [Ph₃Sn(IND)] and [Ph₃Sn(FBP)]. The crystal structure of [Ph₃Sn(IND)] reveals penta-coordination of the central tin atom with almost perfect trigonal bipyramidal geometry with phenyl groups in the equatorial positions and two axially located oxygen atoms belonging to two distinct carboxylato (IND) ligands leading to formation of a coordination polymer with bridging carboxylato ligands. Employing MTT and CV probes, the antiproliferative effects of both organotin(IV) complexes, indomethacin, and flurbiprofen were evaluated on different breast carcinoma cells (BT-474, MDA-MB-468, MCF-7 and HCC1937). [Ph₃Sn(IND)] and [Ph₃Sn(FBP)], unlike the inactive ligand precursors, were found extremely active towards all examined cell lines, demonstrating IC₅₀ concentrations in the range of 0.076-0.200 µM. Flow cytometry was employed to examine the mode of action showing that neither apoptotic nor autophagic mechanisms were triggered within the first 48 h of treatment. However, both tin(IV) complexes inhibited cell proliferation potentially related to the dramatic reduction in NO production, resulting from downregulation of nitric oxide synthase (iNOS) enzyme expression.

Keywords: NO production; anticancer; breast cancer; flurbiprofen; indomethacin; triphenyltin(IV).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Breast Neoplasms* / drug therapy
Carboxylic Acids
Cell Line, Tumor
Female
Flurbiprofen* / pharmacology
Humans
Indomethacin
MCF-7 Cells
Tin

Substances

triphenyltin
Antineoplastic Agents
Tin
Flurbiprofen
Carboxylic Acids
Indomethacin

Grants and funding

This work was financially supported through the program FEM POWER (funded by the operational program ESF Saxony-Anhalt WISSENSCHAFT Chancengleichheit with funds from the European Union; doctoral grant for I.P.), the Graduate School “Building with Molecules and Nanoobjects (BuildMoNa)” and the Research Academy Leipzig.