Synthesis, characterization, crystal structure, DNA and human serum albumin interactions, as well as antiproliferative activity of a Cu(II) complex containing a Schiff base ligand formed in situ from the Cu(II)‐induced cyclization of 1,5‐bis(salicylidene)thiocarbohydrazide

Abstract

The reaction of Cu(OAc)2·H2O with o‐HOC6H4‐C(H)N‐NH‐C(S)‐NH‐NC(H)‐C6H4OH‐o in methanol resulted in the formation of a dinuclear Cu(II) complex [(o‐phen)Cu(HL)Cu(HL)] (1) in the solution where HL2− is a new O−NN− ligand ο−HOC6H4‐normalC()H=normalN‐normalN=truenormalC‐normalS‐normalCfalse(=normalN‐NH⎵false)‐C6H4OH−ο formed in situ from cyclization of the Schiff base and the isolated product was found to be a dimer of 1 forming a tetranuclear compound in solid due to axial coordination of bridging phenolate O− as revealed from X‐ray crystallography. Electronic spectroscopic study using calf thymus DNA as well as fluorescence quenching study of ethidium bromide bound DNA in presence of 1 showed intercalative DNA binding with Kb = 1.12 × 105 M−1 and Kapp = 8.80 × 105 M−1, respectively. This compound was found to be efficient in hydrolytic as well as oxidative DNA cleavage. The binding interaction between complex 1 and human serum albumin (HSA) was investigated using fluorescence emission, absorption, and molecular docking studies. 3D fluorescence studies revealed that HSA structure was altered at secondary and tertiary levels. The binding constant Ka value (~106 M−1) suggested a strong binding affinity of 1 to HSA, and the bimolecular quenching constant kq value (1013 M−1 s−1) suggested a static quenching mechanism operative in the quenching of the intrinsic fluorescence of the protein. Such high kq value may also be accounted by Förster resonance energy transfer (FRET) process. The distance r (3.22 nm) between donor HSA and acceptor complex 1 calculated from FRET theory suggested that they are close to each other. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay with human cervical cancer HeLa cells and human breast cancer MCF7 cells (IC50 = 2.2 and 1.2 μM, respectively) suggested remarkable in vitro anticancer activity of 1. Cell death in HeLa cells was induced via apoptosis as revealed from nuclear staining assays using Hoechst 33342 and acridine orange/propidium iodide dual staining, and apoptosis induction in HeLa cells happened through reactive oxygen species accumulation.

Synthesis, Characterization, Crystal Structure, DNA and HSA Interactions, and Anticancer Activity of a Mononuclear Cu(II) Complex with a Schiff Base Ligand Containing a Thiadiazoline Moiety

“…Synthesis and Characterization. When a methanol solution of Cu(OAc) 2 •H 2 O and 1,10-phenanthroline (1 mmol e a c h ) w a s r e a c t e d w i t h 1 , 5 -b i s ( s a l i c y l i d e n e )thiocarbohydrazide 54 (A, Scheme 1) in the presence of air, enolization (B) followed by cyclization 53 occurred in the Schiff base, forming in situ a new Schiff base containing a thiadiazoline ring (C, Scheme 1) that was found to coordinate to Cu 2+ ions as an O − NN − chelate 53 and was stable along with a water molecule as evident from the fact that this species was detected in the ESI-MS experiment of the compound in CH 3 CN with the major peak at m/z 391.02 (Figure S1A) that corresponds to [ 2.3. IR and Electronic Spectra.…”

Mixed Ligand Mononuclear Copper(II) Complex as a Promising Anticancer Agent: Interaction Studies with DNA/HSA, Molecular Docking, and In Vitro Cytotoxicity Studies

“…Cellular morphology assessment was done using an AO and PI double staining assay. 72 HeLa cells seeded in a 35 mm confocal dish with a density of 1 × 10 6 were placed in a CO 2 incubator overnight. The cells were then treated with three different complex 1 concentrations, and one dish was left untreated to be used as control.…”

“…Cellular morphology assessment was done using an AO and PI double staining assay . HeLa cells seeded in a 35 mm confocal dish with a density of 1 × 10 6 were placed in a CO 2 incubator overnight.…”

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs

“…Thus, inside cells, iron can go from one oxidation state to another under physiological conditions. This redox cycle is also responsible for the toxic ability of iron toward cancer cells, which is accomplished through the stimulation of reactive oxygen species (ROS) formation [ 78 ].…”