Spectro Analytical, Computational and In Vitro Biological Studies of Novel Substituted Quinolone Hydrazone and it’s Metal Complexes

Abstract

Some novel transition metal [Cu (II), Ni (II) and Co (II)] complexes of nalidixic acid hydrazone have been prepared and characterized by employing spectro-analytical techniques viz: elemental analysis, H-NMR, Mass, UV-Vis, IR, TGA-DTA, SEM-EDX, ESR and Spectrophotometry studies. The HyperChem 7.5 software was used for geometry optimization of title compound in its molecular and ionic forms. Quantum mechanical parameters, contour maps of highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) and corresponding binding energy values were computed using semi empirical single point PM3 method. The stoichiometric equilibrium studies of metal complexes carried out spectrophotometrically using Job's continuous variation and mole ratio methods inferred formation of 1:2 (ML) metal complexes in respective systems. The title compound and its metal complexes screened for antibacterial and antifungal properties, exemplified improved activity in metal complexes. The studies of nuclease activity for the cleavage of CT- DNA and MTT assay for in vitro cytotoxic properties involving metal complexes exhibited high activity. In addition, the DNA binding properties of Cu (II), Ni (II) and Co (II) complexes investigated by electronic absorption and fluorescence measurements revealed their good binding ability and commended agreement of K values obtained from both the techniques. Molecular docking studies were also performed to find the binding affinity of synthesized compounds with DNA (PDB ID: 1N37) and "Thymidine phosphorylase from E.coli" (PDB ID: 4EAF) protein targets.

A Photoacoustic Probe for the Imaging of Tumor Apoptosis by Caspase‐Mediated Macrocyclization and Self‐Assembly

“…[18] We found this strategy to be amenable to design fluorescence, [3b] PET, [19] and MRI [20] probes for detecting enzyme activity (e.g., furin and caspase-3) in vivo.T hrough integration with at umor-targeting ligand (i.e., c-RGD) and aP Ai maging dye,w ed emonstrate that 1-RGD can be efficiently delivered and activated by active caspase-3 in apoptotic tumor tissues after intravenous (i.v.) Thef ree d-Cys and CHQ subsequently undergo fast intramolecular condensation to form cyclized product 1-cycl, which is more rigid and hydrophobic (log P = 4.47 for 1-cycl versus À1.38 for 1-RGD), [21] inducing stronger intermolecular interactions (e.g., hydrophobic interaction and p-p stacking) to promote molecular self-assembly into nanoparticles.Nanoparticles containing ah igh density of ICG molecules emit weak NIR fluorescence owing to the aggregation-caused quenching (ACQ) effect, which increases the PA signal by augmenting nonradiative relaxation processes ( Figure 1b). Figure 1a presents the design of 1-RGD,consisting of a2cyano-6-hydroxyquinoline (CHQ) and d-cysteine (d-Cys) residue,acaspase-3-cleavable peptide substrate (DEVD), aglutathione (GSH)-reducible disulfide bond, and aclinically used near-infrared (NIR) dye (indocyanine green, ICG).…”

“…Upon interaction with intracellular GSH and active caspase-3 in apoptotic tumors,t he thiol and amino groups of the d-Cys residue in 1-RGD are uncaged. Thef ree d-Cys and CHQ subsequently undergo fast intramolecular condensation to form cyclized product 1-cycl, which is more rigid and hydrophobic (log P = 4.47 for 1-cycl versus À1.38 for 1-RGD), [21] inducing stronger intermolecular interactions (e.g., hydrophobic interaction and p-p stacking) to promote molecular self-assembly into nanoparticles.Nanoparticles containing ah igh density of ICG molecules emit weak NIR fluorescence owing to the aggregation-caused quenching (ACQ) effect, which increases the PA signal by augmenting nonradiative relaxation processes ( Figure 1b). Thes ize of the nanoparticles is also substantially larger than that of 1-RGD,w hich results in their prolonged retention in apoptotic tumor tissues while un-activated small-molecule probes are washed out from viable tumor tissues;t hus, localized PA signal enhancement in apoptotic regions is achieved to signal caspase-3 activity ( Figure 1c).…”

Equilibrium, DNA binding, docking, and antimicrobial studies of Ni(II) and Cu(II) chelates with 1‐(4′‐nitrobenzoyl)‐3‐thiosemicarbazide

“…Docking of metal chelates with DNA has been carried out in Autodock 4.2. [ 46,47 ] Crystal structure of DNA complexed with Anthracycline Respinomycin D is downloaded from protein data bank (http://www.rcsb.org) pdb id: 1N37; [ 48 ] it is prepared by protein preparation wizard applying OPLS 2005 force field in Schrodinger suite 2010. A grid has been prepared around the intercalation site by selecting the co‐crystallized ligand.…”

Synthesis, characterization and biological activity of mixed ligand chelates of Ni(II) with pyridoxalthiosemicarbazone and dipeptides

“…Molecular Docking studies Docking studies of the interaction of metal complexes with DNA was carried out in Autodock 4.2 as reported. [38,39] Crystal structure of DNA was downloaded from protein data bank (www.rcsb.org)pdb id: 1N37, [40] which was prepared by protein preparation wizard applying OPLS 2005 force field in Schrodinger suite. A grid was prepared around the intercalation site by selecting the cocrystallized ligand.…”