Novel triphenyltin(IV) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation

Marijana P. Kasalović; Sanja Jelača; Žiko Milanović; Danijela Maksimović-Ivanić; Sanja Mijatović; Jelena Lađarević; Bojan Božić; Zoran Marković; Duško Dunđerović; Tobias Rüffer; Robert Kretschmer; Goran N. Kaluđerović; Nebojša Đ. Pantelić

doi:10.1039/D4DT00182F

Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation†

Marijana P. Kasalović,^ab Sanja Jelača,

^c Žiko Milanović,^d Danijela Maksimović-Ivanić,^c Sanja Mijatović,^c Jelena Lađarević,^e Bojan Božić,^f Zoran Marković,

^d Duško Dunđerović,

^g Tobias Rüffer,

^h Robert Kretschmer,

^h Goran N. Kaluđerović

*^a and Nebojša Đ. Pantelić

*^ai

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* Corresponding authors

^a Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Straße 2, 06217 Merseburg, Germany
E-mail: goran.kaluderovic@hs-merseburg.de, pantelic@agrif.bg.ac.rs

^b Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia

^c Department of Immunology, Institute for Biological Research “Siniša Stanković” National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia

^d Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia

^e Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia

^f Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia

^g Institute of Pathology, School of Medicine, University of Belgrade, dr Subotića 1, Belgrade, Serbia

^h Institute of Chemistry, Chemnitz University of Technology, Straße der Nationen 62, D-09111 Chemnitz, Germany

ⁱ Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade, Serbia

Abstract

Three newly synthesized triphenyltin(IV) compounds, Ph₃SnL1 (L1⁻ = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph₃SnL2 (L2⁻ = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph₃SnL3 (L3⁻ = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (¹H, ¹³C and ¹¹⁹Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph₃SnL1 and Ph₃SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph₃SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC₅₀ values fall in the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph₃SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph₃SnL1 showed the potential to reduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.

Dalton Transactions

Novel triphenyltin(iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation†

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Novel triphenyltin(IV) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: in vitro and in vivo evaluation

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