Structural data of DNA binding and molecular docking studies of dihydropyrimidinone transition metal complexes

A series of some novel copper complexes derived from Biginelli condensation of DHPHS. The ligand and its transition metal complexes show more antimicrobial activities which was substantiated by molecular docking studies. Transition metal complexes four possess antioxidant properties supported by the DNA-binding, cleavage, and viscosity measurement (Prasad et al., 2011) [1]. The in Silicon DNA binding reveals copper complex is bound to be Minor groove and other manganese, cobalt, nickel complexes are bound to the Major groove portion of DNA through hydrogen bonds and hence copper (II), manganese (II), cobalt (II), nickel (II) complexes are called Minor groove and Major groove binder respectively. The DNA cleavage studies of metal complexes presented more protruding activity in the attendance of H2O2 associated to that in the absence of H2O2. In continuance of our ongoing research on DNA binding and cleavage happenings of transition metal complexes, in this paper we obtainable the synthesis, characterization and DNA cleavage activities.


Specifications
DNA binding studies of metal complexes ( Mn (II), Co (II), Ni (II), Cu (II)) to DNA helix has been characterized through absorption spectral titrations, significant hypochromism with a red shift of 10 nm (bathochromism) of absorption band implicates intercalative mode of binding and is likely that the all complexes with aromatic chromophore stabilizes the DNA duplex. The lower electropositive character of the metal which increases the binding mode with DNA. The electropositive character of the metal decreases as the following order: Cu(II) oNi(II). Increase in viscosity of DNA as much for all M(II) complexes is observed, this increase in separation of base pairs at intercalation sites and hence an increase in DNA contour length, results from the viscosity experiments confirm the mode of these compounds intercalating into DNA base pairs. The double-stranded DNA tends to gradually dissociate to single strands on increase in the solution temperature and generates a hyperchromic effect on the absorption spectra of DNA bases, insertion of planar aromatic ligand in between the DNA base pairs via intercalation cause stabilization of base stack and hence raises the melting temperature of the double-stranded DNA. Introduction of metal group (Mn, Co, Ni, Cu) in the ligand system markedly increases the antioxidant efficient due to decreased electropositive character of metals. The activity was found in the following order MnL 2 oCoL 2 oNiL 2 oCuL 2 . Redox behaviour of the complexes responsible for its antioxidant activity, difference in reactivity of the synthesized complexes may be attributed to the coordination environment and the redox potential of the couple Cu I /Cu II in copper(II) complex during the catalytic cycle. Copper complex had better glide energy and docking score compared with respect to Cocrystal ligand 3U2D-08B, 1AI9-NDP, 4CMT-GWH, 2FOM, 3OYA-RLT. Copper complex shows interaction of hydrogen bond residue and hydrophobic interaction shows with various pathogenic protein results better activity drug which are applicable through pharmaceutical and medicinal field Data source location Complex shows interaction of hydrogen bond residue and hydrophobic interaction with various pathogenic protein result better activities thorough antimicrobial, anticancer, antiviral, antiinflammatory, antigen due to. So our research demonstrates that the imines exhibit their ulcer healing properties probably due to their antioxidant action.

Data
A new series of transition metal complexes hydrodynamic measurements central rings of metal (M ¼Mn (II), Co(II), Ni(II), Cu(II) and imine, heterocyclic keto groups are involved in intercalative mode of DNA binding, increase in viscosity of DNA is ascribed to the intercalative binding mode of the copper complexes this could cause the effective length of the DNA to increase. The thermal behaviour of CT-DNA in the presence of complexes gave insight into their conformational changes when temperature is raised and information about the interaction strength of the complexes with DNA. The double -stranded DNA tends to gradually dissociate to single strands on increase in the solution temperature and generates a hyperchromic effect on the absorption spectra of DNA bases. DNA melting curves obtained in the presence of DNA reveal a monoplastic and irreversible melting of the DNA strands. The insertion of planar aromatic ligand in between the DNA base pairs via intercalation cause stabilization of base stack and hence raises the melting temperature of the double-stranded DNA. Metal complexes were able to convert super coiled DNA into open circular DNA. Metallo complexes bound hydroxyl radical or a peroxo species generated from the co-reactant H 2 O 2 . The DNA cleavage studies of metal complexes showed more prominent activity in the presence of H 2 O 2 compared to that in the other metal complexes. All metal complexes showed significant nuclease activity in the presence of H 2 O 2.

Absorption titration experiments
The concentration of CT-DNA was determined from the absorption intensity at 265 nm with ε value of 6620 (mol L À 1 ) À 1 . Absorption titration experiments were made using different concentration of CT-DNA, while keeping the complex concentration constant. Each sample solution was scanned from 200 to 600 nm.

Viscosity experiments
Viscosity experiments were conducted on the Ub-belohde viscometer, immersed in a water bath maintained at 257 0.1°C.

Gel electrophoresis
The DNA cleavage experiment was conducted using CT DNA by gel electrophoresis with the corresponding metal complex in the presence of H 2 O 2 as an oxidant.

Superoxide dismutase activity (SOD)
The superoxide dismutase activity (SOD) of the Mn(II), Co(II), Ni(II), Cu(II) complexes were evaluated using alkaline DMSO as source of superoxide radicals (O 2̇̅ ̅ ) generating system in association with nitro blue tetrazolium (NBT) as a scavenger of superoxide.

Protein structure preparation
The x-ray crystal structure of proteins such as S.aureus Gyr B ATPase, Candida albicans dihydrofolate reductase, phospholipase, Human Anaplastic lymphoma kinase, Dengue Virus NS 2 B/NS 3 protease, retroviral integrase are obtained from the Research collaborator for Bioinformatics (RCSB) Protein Data Bank are used in this study.

Docking protocol
Totally all the docking calculation results are performed by "Extra precision" (XP) mode of Glide program (Figs. 1-7 and Tables 1-4).       Table 3 Interaction of ligand and copper complex with 3U2D bacterial protein.

S.
No.

Compound Protein target
Docking score