DNA targeting polyaza macrobicyclic dizinc(ii) complexes promoting high in vitro caspase dependent anti-proliferative activity against human carcinoma cancer cells

Abstract

A series of macrobicyclic dizinc(II) complexes [Zn(2)L(1-2)B](ClO(4))(4) (1-6) have been synthesized and characterized (L(1-2) are polyaza macrobicyclic binucleating ligands, and B is the N,N-donor heterocyclic base (viz. 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen)). The DNA and protein binding, DNA hydrolysis and anticancer activity of these complexes were investigated. The interactions of complexes 1-6 with calf thymus DNA were studied by spectroscopic techniques, including absorption, fluorescence and CD spectroscopy. The DNA binding constant values of the complexes were found to range from 2.80 × 10(5) to 5.25 × 10(5) M(-1), and the binding affinities are in the following order: 3 > 6 > 2 > 5 > 1 > 4. All the dizinc(II) complexes 1-6 are found to effectively promote the hydrolytic cleavage of plasmid pBR322 DNA under anaerobic and aerobic conditions. Kinetic data for DNA hydrolysis promoted by 3 and 6 under physiological conditions give observed rate constants (k(obs)) of 5.56 ± 0.1 and 5.12 ± 0.2 h(-1), respectively, showing a 10(7)-fold rate acceleration over the uncatalyzed reaction of dsDNA. Remarkably, the macrobicyclic dizinc(II) complexes 1-6 bind and cleave bovine serum albumin (BSA), and effectively promote the caspase-3 and caspase-9 dependent deaths of HeLa and BeWo cancer cells. The cytotoxicity of the complexes was further confirmed by lactate dehydrogenase enzyme levels in cancer cell lysate and content media.

Nuclease activity and interaction studies of unsymmetrical binuclear Ni(ii) complexes with CT-DNA and BSA

“…Therefore, the second Ni(II) ion reduced at higher negative potentials. 105 The absorption spectra of complex 1 and 5 in the absence and presence of CT-DNA are shown in Fig. The distortion around the geometry also increases.…”

Bio-relevant complexes of novel N2O2 type heterocyclic ligand: Synthesis, structural elucidation, biological evaluation and docking studies

“…After the addition of DNA, the emissive band is started to appear and its intensity is increased upon increasing DNA concentration due to the strong intercalation between the adjacent base pairs of DNA. The enhancement of emission intensity can be quenched by the addition of another molecule, which can bind DNA via intercalative mode by displacing EB [29]. The emission spectra of EB bound to DNA both in presence and absence of [Cu(H 2 L)] as shown in Fig.…”

Hexanuclear Zn(II) and Mononuclear Cu(II) Complexes containing imino phenol ligands: Exploitation of their Catalytic and Biological Perspectives

“…Nonetheless, copper and zinc ions have remarkable affinity to bind with these types of Schiff base ligands through chelation . In past decades, transition metal complexes comprising of phenolic moieties in the ligand skeleton were reported owing to their appreciable binding and cleaving abilities towards DNA …”