Synthesis, characterization and in vitro anticancer, DNA binding and cleavage studies of Mn (II), Co (II), Ni (II) and Cu (II) complexes of Schiff base ligand 3‐(2‐(1‐(1H‐benzimidazol‐2‐yl)ethylidene)hydrazinyl)quinoxalin‐2(1H)‐one and crystal structure of the ligand
Abstract:A Schiff base ligand, 3‐(2‐(1‐(1H‐benzimidazol‐2‐yl)ethylidene)hydrazinyl)quinoxalin‐2(1H)‐one (BZHQO), has been synthesized by the condensation of 3‐hydrazinylquinoxalin‐2(1H)‐one and 1‐(1H‐benzoimidazol‐2‐yl) ethanone and characterized using spectral and single‐crystal X‐ray analyses. Mn (II), Co (II), Ni (II) and Cu (II) complexes of the BZHQO ligand have been synthesized and characterized. The interactions of the ligand and its metal complexes with calf thymus DNA have been investigated using absorption sp… Show more
“…Therefore, complex 1 was selected for further studies. Additionally, when compared to other Cu II complexes containing analogous ligands, complex 1 has already been shown to stand out as one of the most active copper-based compounds 25 , 26 with high selectivity 22 , as it can be confirmed by the present work.…”
The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.
“…Therefore, complex 1 was selected for further studies. Additionally, when compared to other Cu II complexes containing analogous ligands, complex 1 has already been shown to stand out as one of the most active copper-based compounds 25 , 26 with high selectivity 22 , as it can be confirmed by the present work.…”
The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.
“…[15] Since the first reported studies on the biological activity of cobalt complexes in 1952, many cobalt complexes of biological interest have been reported, with the most structurally characterized showing antitumor, antiproliferative, antimicrobial, and antifungal activity. [16][17][18][19][20] In our experiment, a novel CP based on Co(II) has been generated in the existence of a second N-donor ligand 3,3 0 -bipyridine (3,3 0 -bpy) utilizing 4,4 0 ,4 00 -phosphanetriyltribenzoic acid (H 3 tpp) as the tritopic connector under conditions of solvothermal reaction, and its chemical formula is [Co 3 (tpp) 2 (3,3 0 -bpy)]Á 7DMF (1). The product acquired was completely investigated using powder X-ray diffraction (PXRD), thermogravimetric analyses, infrared radiation (IR) spectra, and elemental analysis (EA), as well as the diffraction of a single-crystal X-ray.…”
A novel coordination polymer based on Co(II) has been generated utilizing the 4,4′,4″‐phosphanetriyltribenzoic acid (H3tpp) as the tritopic connector in the existence of a second N‐donor ligand 3,3′‐bipyridine (3,3′‐bpy) under the solvothermal reaction conditions, and its chemical formula is [Co3(tpp)2(3,3′‐bpy)]·7DMF (1). Moreover, under ultraviolet irradiation, complex 1 has high photocatalytic activities for methylene blue degradation, and its photodegradation performance does not show much reduction after three cycles of experiments. Furthermore, the compound's biological activity against the mania was assessed, and the protentional mechanism was discussed. First, the neuroregulin1 content in the hippocampus was detected via enzyme‐linked immunosorbent assay to evaluate the compound's treatment activity on mania. Then, the ErbB4 relative expression levels were detected using real‐time reverse transcription‐polymerase chain reaction. The carboxyl groups have been confirmed to be responsible for all the binding interactions formed by molecular docking simulation.
“…Gel electrophoresis of plasmid DNA resulted in the migration of fastest moving supercoiled form, Form I to relaxed nicked form, Form II, along with the appearance of slow-moving linearized form, Form III of DNA migrating between supercoiled and nicked forms, which indicated lethal double-stranded cleavage of DNA (Figure S9). [56] The concentration-dependent DNA cleavage assay was performed to evaluate the affinity of complex 1 towards supercoiled (SC) DNA in the absence of any reducing agent. Moreover, complex 1 showed efficient cleavage at the micromolar concentration of 15 μM (lane 4) i. e., conversion of Form I to Form II to Form III takes place.…”
A 3-formyl-chromone-appended zinc(II) intercalator drug candidate of the formulation [bis(chromone)(H 2 O) 2 Zn(II)] was prepared as a potent anticancer agent and thoroughly characterized by multi-spectroscopic and single X-ray crystallographic studies. Preliminary binding studies of complex 1 with ct-DNA/tRNA were carried out employing various complementary biophysical techniques and the corroborative results of these experiments suggested strong binding propensity via intercalation binding mode towards ct-DNA/tRNA therapeutic targets, with higher preference for tRNA as quantified by binding constant { K b , K and K sv } parameters. The cleavage studies with pBR322 DNA were performed which implied that 1 cleaved the DNA by hydrolytic cleavage pathway which was further validated by T4 religation assay. Moreover, 1 was found to exhibit the tRNA cleavage behavior in a concentration and time-dependent manner. The cytotoxicity of complex 1 was evaluated against Huh-7, DU-145 and the PNT2 cell lines by MTT assay. A dose-dependent growth inhibition of the Huh-7 and DU-145 cells at low micromolar concentrations was observed and in another set of experiments, lipid peroxidation & glutathione (GSH) depletion were induced in the presence of the tested drug candidate. Interestingly, drug candidate 1 demonstrated selective cytotoxic activity for the DU-145 cancer cell line with LC 50 value of 3.2 μM which was further visualized by confocal microscopy.
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