Bis(thiosemicarbazone)copper(I) Complexes as Prospective Therapeutic Agents: Interaction with DNA/BSA Molecules, and In Vitro and In Vivo Anti‐Proliferative Activities

Abstract

A series of six new bis(thiosemicarbazone)copper(I) complexes of the type [Cu(L1–6)2Cl] (1−6) were synthesized and characterized. The complexes adopted trigonal planar ′Y′ shaped geometry coordinating through two thione sulphur atoms of two ligand molecules and one chloride ion. All the complexes intercalatively bind with calf thymus DNA (CT−DNA) as evidenced by spectral and molecular docking studies. The absorption and emission spectral techniques confirmed the strong interaction of the complexes with BSA via static quenching mode. The complexes efficiently cleave pBR322 DNA via hydrolytic pathway, and significantly interact with epidermal growth factor receptor. All the complexes were assessed for their anti‐proliferative activity, in which the complexes 2, 3 and 4 containing methyl, methoxy and hydroxyl groups, respectively, showed significant activity. The complexes induce apoptosis in EAC cells as evidenced by acridine orange (AO)/ethidium bromide (EB), Hoechst 33258 and propidium iodide (PI) staining methods, and cell cycle analysis. Cellular uptake studies revealed the ability of the complexes to go into the cytoplasm and accumulation in the cell nuclei. The complexes are involved in the generation of reactive oxygen species (ROS), mitochondrial mediated and caspase‐dependent apoptosis. Further, using a female Swiss albino mice model, we found that the complexes 2 and 3 inhibited Ehrlich ascites carcinoma (EAC) tumour cell growth in vivo.

Unusual coordination mode of aroyl/acyl thiourea ligands and their π‐arene ruthenium (II) piano‐stool complexes: Synthesis, molecular geometry, theoretical studies and biological applications

“…Eventually, we have found that the thiourea ligand and its Ru‐ p ‐cymene complex displayed a rather unusual coordination mode where they form a strained four‐membered ring. This type of coordination mode was also known for some thiosemicarbazones . The new coordination mode of aroyl/acyllthiourea ligands along with the five different coordination modes was shown in Figure .…”

Insight into the Anticancer Activity of Copper(II) 5-Methylenetrimethylammonium-Thiosemicarbazonates and Their Interaction with Organic Cation Transporters

“…Copper(I) has a strong preference for tetrahedral coordination geometry [ 68 , 69 ] even though linear [ 70 ] and 3-coordinate geometry has also been documented [ 71 , 72 ]. The potentially tridentate thiosemicarbazones, like HL R studied in this work, are unable to accommodate tetrahedral copper(I) [ 68 ].…”

Anticancer Potency of Copper(I) Complexes Against a Range Cancer Cell Lines: A Review

“…The thiocarbamides with two different substituents on Natoms exhibit hydrogen bonding between the carbonyl group of substituent and HN group of amide that helps the existence of coordinate covalent bond directly through Satoms, increases lipophilicity and anticancer potency of ligands and their complexes via effective interaction with DNA (Xian et al, 2004;Saeed et al, 2010;Singh et al, 2015;Saswati et al, 2015;Mahendiran et al, 2018b;Pandey et al, 2018). Copper(I) ion, obtained by the reduction of copper(II) ion with metallo-reductase at the cell surface of living organisms, before uptake into the cell can be transported into the living cells by their specific transporters Marzano et al, 2009).…”

“…Copper(I) complexes dissociate partially by generating an empty site on Cu + ions that can facilitate the complexes to interact with the biological target (Santini et al, 2013). The modification in the structure of organic moiety by different substituents affects the anticancer activity of copper complexes (Saswati et al, 2015;Mahendiran et al, 2018b;Singh et al, 2021b).…”