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 .…”

Cu(i) diimine complexes as immobilised antibacterial photosensitisers operating in water under visible light

“…[56][57][58][59][60] Cu(I) complexes are being increasingly used as photosensitisers in photocatalysis, 24,25,30,51,[61][62][63][64][65][66][67][68][69][70][71][72][73] and dyes-sensitised solar cells. 74 They are also used as antitumor [75][76][77][78] and antibacterial agents [79][80][81][82][83][84][85] due to their innate dark toxicity. However, utilisation of their photosensitisation properties for PDT or antimicrobial PDT has been overlooked so far.…”

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 ].…”