o:33085 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 en 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. Keywords: heteronuclear complexes; 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine; structure–reactivity correlation; cytotoxic activity; colorectal cancers 1552099 10.3390/ijms25053027 1552101 1422-0067 2024-03-09T10:00:02.816Z 44 no 46 Samir Vučelj 0009-0002-5743-0346 Rušid Hasić Državni univerzitet u Novom Pazaru person 0009-0001-1740-9764 Darko Ašanin person 0000-0003-1098-400X Biljana Šmit person Angelina Caković person Jovana Bogojeski person Marina Ćendić Serafinović person Bojana Simović Marković person Bojan Stojanović person Sladjana Pavlović person Isidora Stanisavljević person Irfan Ćorović person Milica Dimitrijević Stojanović person Ivan Jovanović person Tanja V. Soldatović Državni univerzitet u Novom Pazaru person 0000-0003-3010-6503 Bojana Stojanović person application/pdf 6450838 https://phaidrabg.bg.ac.rs/o:33085 no yes 16 70 92000001 20A01 International Journal of Molecular Sciences 25 3027 1 27 2024