application/pdf 6450838 bytes International Journal of Molecular Sciences 25(3027) Vučelj, Samir Hasić, Rušid Ašanin, Darko Šmit, Biljana Caković, Angelina Bogojeski, Jovana Ćendić Serafinović, Marina Simović Marković, Bojana Stojanović, Bojan Pavlović, Sladjana Stanisavljević, Isidora Ćorović, Irfan Dimitrijević Stojanović, Milica Jovanović, Ivan Soldatović, Tanja V. Stojanović, Bojana eng 2024 info:eu-repo/semantics/article http://creativecommons.org/licenses/by/4.0/legalcode https://phaidrabg.bg.ac.rs/o:33085 doi:10.3390/ijms25053027 ISSN: 1422-0067 Modes of Interactions with DNA/HSA Biomolecules and Comparative Cytotoxic Studies of Newly Synthesized Mononuclear Zinc(II) and Heteronuclear Platinum(II)/Zinc(II) Complexes toward Colorectal Cancer Cells Keywords: heteronuclear complexes; 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine; structure–reactivity correlation; cytotoxic activity; colorectal cancers Abstract: A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4,4-tri-tert-butyl-2,2:6,2-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4’-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(μ-4,4’-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2-C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.