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

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

Ivana Predarska  1   2 , Mohamad Saoud  3 , Ibrahim Morgan  3 , Peter Lönnecke  1 , Goran N Kaluđerović  2   3 , Evamarie Hey-Hawkins  1
Affiliations

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

Ivana Predarska et al. Biomolecules. .

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).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Organotin(IV) carboxylates: triphenyltin(IV) indomethacinate, [Ph3Sn(IND)], and triphenyltin(IV) flurbiprofenate, [Ph3Sn(FBP)].
Figure 2
Figure 2
Section of the polymeric structure of [Ph3Sn(IND)]; hydrogen atoms and solvent molecules are omitted for clarity; thermal ellipsoids are set at 50% probability level.
Figure 3
Figure 3
Helical chain structure of [Ph3Sn(IND)], propagation via O → Sn coordination. Bonds forming the basis of the helix are highlighted in pink.
Figure 4
Figure 4
Capacity of organotin(IV) complexes ([Ph3Sn(IND)] and [Ph3Sn(FBP)]) and cisplatin to induce apoptotic cell death—early and late apoptotic cells (after 48 h treatment).
Figure 5
Figure 5
Effect of organotin(IV) complexes ([Ph3Sn(IND)] and [Ph3Sn(FBP)]) and cisplatin on BT-474 cells: (A) caspase activation, (B) ROS/RNS production, (C) NO production, and (D) cell proliferation potential.
Figure 6
Figure 6
Autophagy induction in BT-474 cells upon 48 h treatment with organotin(IV) complexes ([Ph3Sn(IND)] and [Ph3Sn(FBP)]) and cisplatin.
See this image and copyright information in PMC

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