Pharmaceutical manifestation of Knoevenagel condensed metal (II) complexes through virtual, in vitro and in vivo assessments.

Sulphur containing compounds possess a great deal of interest due to wide range of beneficial activities towards biotic species. This work also deals with the study of biological examination of newly synthesized sulphur containing Cu(II) and Zn(II) complexes derived from (E)-4-(phenylimino)-3-((E)-1-(phenylimino)ethyl)pent-2-ene-1-thiol Schiff bases. Moreover, the DNA nuclease efficiency of the synthesized metal complexes is studied by UV absorption studies, Fluorescence studies, Viscosity and CV titrations which confirm the intercalative mode of binding. Pharmacokinetic studies and drug like activity of these compounds are screened with the help of SWISS ADME online freeware. Their morphological nature is corroborated by various spectral techniques. Optimized geometry and biologically accessible nature of the synthesized compounds are investigated by Gaussian 09 W software. Interestingly, molecular docking studies are carried out against cancer DNA and 6J10 cancer cell. Anti-inflammatory and in vitro antioxidant activities have been studied to validate the theoretical prediction. Based on these preliminary pharmacological activities, the in vitro cytotoxicity and in vivo antitumor activities are examined using MCF-7, HeLa, Hep-2, HepG-2 and Ehrlich ascites carcinoma (EAC) cell lines. All the above examinations reveal that the nitro substituted transition metal complexes possess higher biological bustle.Communicated by Ramaswamy H. Sarma.

Cu(II) and Zn(II) complexes incorporating Knoevenagel ß-diketimine Schiff basesThe quantum mechanical examinations using Gaussian 09W softwareInvestigation of possible interactions with DNA by Molecular docking studiesIn silico, in vitro and in vivo analyses of the synthesized compounds.

Synthesis, characterization, in vitro, in silico and in vivo investigations and biological assessment of Knoevenagel condensate ß-diketone Schiff base transition metal complexes.

A novel Schiff base ligand was synthesized by the Knoevenagel condensation of ß-diketone (obtained from substituted Curcumin and Cuminaldehyde) and 4-amino antipyrine. Metal complexes were made from this Schiff base by reacting with metal salts such as Cu(II), Ni(II), Ru(III), VO(IV), and Ce(IV). Physicochemical approaches such as UV-Vis, FT-IR, NMR, EPR, and Mass spectroscopy were used to determine the geometry of the complexes. The thermodynamic stability and biological accessibility of the complexes were investigated using density functional theory (DFT) calculations at the B3LYP/6-31G(d) level. A molecular docking analysis was also performed on 1BNA receptor. Both the Schiff base ligand and metal complexes interacted well to this protein receptor. All metal complexes have a significant potential to bind to CT DNA via the intercalation mechanism. All the in vivo and in vitro screening studies showed that the complexes exhibit higher activities than the free Schiff base.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization, ADMET, in vitro and in vivo studies of mixed ligand metal complexes from a curcumin Schiff base and lawsone.

Complexes are currently synthesized from plant origin because of their therapeutic effect against certain diseases with toxicity. Hence, in this work, four new transition metal(II) mixed ligand complexes have been synthesized using a curcumin Schiff base (primary ligand) and lawsone (as co-ligand). The geometry of these complexes was explored by elemental analyses, molar conductance, thermal analysis, magnetic moment values, IR, NMR, Mass, electronic and EPR spectral studies. Electronic absorption titrations, viscosity measurements and molecular docking studies reveal that all the metal complexes interact with the CT DNA by groove binding. Among all the complexes, the copper(II) complex (complex 1) exhibits a higher Kb value (3.5 × 10-4 M) which reveals that it has a strong binding efficiency toward the CT DNA. The complexes also possess strong DNA cleavage efficiency. Cytotoxicity investigations on Artemia salina show that all the complexes possess higher cytotoxic effect than the ligand. Moreover, all the metal complexes have better antimicrobial efficacy than the ligand. Swiss ADME, PASS and pkCSM online softwares are helpful to predict the pharmacokinetic and biological actions of the curcumin Schiff base. Theoretical results obtained from the in silico study are experimentally corroborated by in vivo anti-inflammatory screening study. All the above studies demonstrate that the copper complex possesses biological activity similar to that of the drug like molecules. Research Highlights Synthesis and characterization of four novel transition mixed ligand complexes using plant moieties Promising in vivo anti-inflammatory agents and in vitro DNA metallonucleases Cytotoxicity investigation on Artemia salina Higher cytotoxic effect for the complexes than the ligand Identification of copper(II) complex as lead like molecule among all.

In silico and in vitro studies of transition metal complexes derived from curcumin-isoniazid Schiff base.

A series of transition metal complexes have been synthesized from biologically active curcumin and isoniazid Schiff base. They are characterized by various spectral techniques like UV-Vis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectroscopies. Moreover, elemental analysis, magnetic susceptibility and molar conductivity measurements are also carried out. All these data evidence that the metal complexes acquire square planar except zinc(II) which adopts a tetrahedral geometry, and they are non-electrolytic in nature. Groove mode of binding between the calf thymus DNA (CT DNA) and metal complexes is confirmed by electronic absorption titration, viscosity and cyclic voltammetry studies. In addition to that, all the metal complexes are able to cleave pUC 19 DNA. Optimized geometry and ground-state electronic structure calculations of all the synthesized compounds are established out by density functional theory (DFT) using B3LYP method which theoretically reveals that copper(II) complex explores higher stability and higher biological accessibility. This is experimentally corroborated by antimicrobial studies. In silico Absorption, Distribution, Metabolism, Excretion (ADME) studies reveal the biological potential of all synthesized complexes, and also biological activity of the ligand is predicted by PASS online biological activity prediction software. Molecular docking studies are also carried out to confirm the groove mode of binding and receptor-complex interactions.