Antioxidant and Biochemical Activities of Mixed Ligand Complexes

Novel 4-aminoantipyrine based mixed ligand metal complexes with the Schiff bases ofL¹(L¹-4(furanylmethyleneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one and L²/ L³/ L⁴are 2-(2-chlorobenzylideneamino)phenol, 2-(3-chlorobenzylideneamino)phenol, 2-(4-chlorobenzylideneamino)phenol were synthesized. The structures of the mixed ligand complexes were established by analytical and spectral techniques. They were screened for in vitro antimicrobial activity against bacteria and fungi by disc diffusion method. The interaction of metal complexes with CT-DNA was investigated by UV–vis, cyclic voltammetry, viscosity and thermal denaturation studies.DNA interaction studies suggest that metal complex binds to calf thymus DNA (CT-DNA) through intercalation mode. Superoxide dismutase activity of these complexes has also been studied. The free ligands and their metal complexes have been tested for in vitro antioxidant activity by the reduction of 1,1-diphenyl-2-picryl hydrazyl (DPPH).The antioxidant activities of the complexes were studied and compared with the activity of ascorbic acid. Cu(II) complex showed superior antioxidant activity than other complexes. The solvatochromic behaviour of complexes was also performed in various solvents.     

Carboxylic Acid f-MWCNT/Graphite and Safranin O/Graphite Based Voltammetric Sensors for Norfloxacin Detection

A well-established electrode modifier, i. e., carboxylic acid (CA) functionalized-multiwalled carbon nanotubes (f-MWCNT), and a less explored safranin O (SFO) were fabricated on cuboidal graphite electrodes to develop two different voltammetric sensors for norfloxacin‘s electrochemical detection. The developed CA f-MWCNT/graphite electrode and SFO/graphite showed a linear range of 3.10×10⁻⁷ to 3.13×10⁻⁵ M and 2.50×10⁻⁸ to 4.06×10⁻⁷ M with a limit of detection of 1.60×10⁻⁸ and 4.80×10⁻⁹ M, respectively. The practical applicability was tested in the spiked hospital wastewater, milk, and orange juice. It showed that the SFO could be a potential modifier for rapid, simple, and sensitive voltammetric detection of norfloxacin.     

Arenes and Heteroarenes C−H Functionalization Under Enabling Conditions: Electrochemistry,Photoelectrochemistry & Flow Technology

C−H bond functionalization generates molecular complexity in single-step transformation. However, the activation of C−H bonds requires expensive metals or stoichiometric amounts of oxidizing/reducing species. In many cases, they often require pre-functionalization of starting molecules. Such pre-activating measures cause waste generation and their separation from the final product is also troublesome. In such a scenario, reactions activating elements generating from renewable energy resources such as electricity and light would be more efficient, green, and cost-effective. Further, incorporation of growing flow technology in chemical transformation processes will accelerate the safer accesses of valuable products. Arenes & heteroarenes are ubiquitous in pharmaceuticals, natural products, medicinal compounds, and other biologically important molecules. Herein, we discussed enabling tools and technologies used for the recent C−H bonds functionalization of arenes and heteroarenes.     

Ground state and excited state dipole moments of alkyl substituted para-nitroaniline derivatives

The ground state and excited state dipole moment of a series of alkyl substituted para-nitroaniline derivatives is reported. Ground state dipole moment was determined by the Debye-Guggenheim method and the excited state dipole moment was estimated using the solvatochromic method. For all molecules under investigation, the excited state dipole moment was found to be higher than the ground state dipole moment. The molecules exhibited positive solvatochromism.     

Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines

A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts.

N-Alkylpyridinium salt of chiral amines undergoes phosphite mediated stereoretentive migrations to generate chiral alkylpyridines. The role of phosphite on reactivity and stereoselectivity were examined to achieve a catalytic asymmetric version.     

A novel microextraction by packed sorbent–gas chromatography procedure for the simultaneous analysis of antiepileptic drugs in human plasma and urine

A simple, accurate, and sensitive microextraction by packed sorbent–gas chromatography‐mass spectrometry method has been developed for the simultaneous quantification of four antiepileptic drugs; oxcarbazepine, carbamazepine, phenytoin, and alprazolam in human plasma and urine as a tool for drug monitoring. Caffeine was used as internal standards for the electron ionization mode. An original pretreatment procedure on biological samples, based on microextraction in packed syringe using C₁₈ as packing material gave high extraction yields (69.92–99.38%), satisfactory precision (RSD < 4.7%) and good selectivity. Linearity was found in the 0.1–500 ng/mL range for these drugs with limits of detection (LODs) between 0.0018 and 0.0036 ng/mL. Therefore, the method has been found to be suitable for the therapeutic drug monitoring of patients treated with oxcarbazepine, carbamazepine, phenytoin, and alprazolam. After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. A comparison of the detection limit with similar methods indicates high sensitivity of the present method over the earlier reported methods. The present method is applied for the analysis of these drugs in the real urine and plasma samples of the epileptic patients.     

Novel micro-extraction by packed sorbent procedure for the liquid chromatographic analysis of antiepileptic drugs in human plasma and urine

A method for the simultaneous determination of the antiepileptic drugs, phenobarbital (PHB), phenytoin (PTN), carbamazepine (CBZ), primidone (PRM) and oxcarbazepine (OXC) in human plasma and urine samples by using micro‐extraction in a packed syringe as the sample preparation method connected with LC/UV (MEPS/LC/UV) is described. Micro‐extraction in a packed syringe (MEPS) is a new miniaturized, solid‐phase extraction technique that can be connected online to gas or liquid chromatography without any modifications. In MEPS approximately 1 mg of the solid packing material is inserted into a syringe (100–250 μL) as a plug. Sample preparation takes place on the packed bed. The bed can be coated to provide selective and suitable sampling conditions. The new method is very promising, easy to use, fully automated, inexpensive and quick. The standard curves were obtained within the concentration range 1–500 ng/mL in both plasma and urine samples. The results showed high correlation coefficients (R²>0.988) for all of the analytes within the calibration range. The extraction recovery was found to be between 88.56 and 99.38%. The limit of quantification was found to be between 0.132 and 1.956 ng/mL. The precision (RSD) values of quality control samples (QC) had a maximum deviation of 4.9%. A comparison of the detection limits with similar methods indicates high sensitivity of the present method. The method is applied for the analysis of these drugs in real urine and plasma samples of epileptic patients.     

Bézier variant of Baskakov-Beta-Stancu operators

In the year 1994, Gupta (Approx Theory Appl (N.S.) 10(3):74–78, 1994) introduced the integral modification of well known Baskakov operators with weights of Beta basis functions and obtained better approximation over the usual Baskakov Durrmeyer operators. The rate of convergence for Bézier variant of these operators for functions of bounded variations were discussed in Gupta (Int J Math Math Sci 32(8):471–479, 2002). The present paper is the extension of the previous work, here we consider the Bézier variant of Baskakov-Beta-Stancu operators. We estimate the rate of convergence of these operators for the bounded functions. In the end of the paper we suggest an open problem.     

In Silico Molecular Docking Analysis of Karanjin against Alzheimer’s and Parkinson’s Diseases as a Potential Natural Lead Molecule for New Drug Design,Development and Therapy

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski’s drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer’s animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.