Design, synthesis, characterization and in vitro, in vivo and in silico antimicrobial and antiinflammatory activities of a new series of sulphonamide and carbamate derivatives of a nebivolol intermediate.

A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.

A novel horseradish peroxidase biosensor towards the detection of dopamine: a voltammetric study.

A polymerized film of glycine (Gly) was prepared on the surface of carbon paste electrode (CPE) through the cyclic voltammetry (CV) technique. A novel biosensor for the determination of dopamine (DA) has been constructed based on horseradish peroxidase (HRP) and multiwalled carbon nanotubes (MWCNTs) immobilizing on Poly (Gly)/CPE through silica sol-gel (SiSG) entrapment. CV measurements were employed in order to understand the feasibility of poly (Gly) as an electron carrier between the immobilized peroxidase and the surface of CPE. By using differential pulse voltammetry (DPV) the calibration curves of DA was obtained in the range of 15-865 µM. The limit of detection (LOD) and limit of quantification (LOQ) of DA was found to be 6×10⁻7 M and 2×10⁻6 M respectively. The apparent Michaelis-Menten constant (Km(app)) was found to be 0.5 mM and illustrated that the good biological activity of the fixed enzyme. Electrochemical impedance spectroscopy (EIS) results confirmed the rapid electron transfer and also the immobilization of enzyme on the electrode surface. The biosensor showed high sensitivity, selectivity and reproducibility. This method has been used to determine DA in the presence of various interferences and in clinical preparations.

Differential pulse adsorptive stripping voltammetric determination of simeton in its formulations and vegetables.

A sensitive adsorptive stripping voltammetric method for the determination of simeton with universal buffer solution has been described. The method was based on the adsorption accumulation of simeton at a hanging mercury drop electrode. The overall reduction process is under controlled diffusion. The adsorptive peak was observed at -0.8 V vs SCE in acidic solution 2

Study of the voltammetric behaviour of the ethalfluralin and methalpropalin and its determination in environmental matrices at hanging mercury drop electrode.

An electroanalytical method has been developed for the determination of the herbicides ethalfluralin[N-ethyl-N-(2-methyl-2-propenyl)-2,6-dinitro-4-(trifluoromethyl) bezenamine] and methalpropalin [N-(2-methyl-2-propenyl)-2, 6-dinitro-N-propyl-4 (trifluoromethyl) benzenamine] by differential pulse adsorptive stripping voltammetry (DP-AdSV) on a hanging mercury drop electrode (HMDE) with universal buffer as supporting electrolyte. The optimum adsorption conditions were found to be pH 6.0, an accumulation potential of -0.6 V (HMDE vs SCE), an accumulation time of 80 s. and scan rate 45 mVs(-1). Calibration curve is linear in the range 1.30 x 10(-9) to 1.32 x 10(-5) M of ethalfluralin and 1.13 x 10(-5) to 2.0 x 10(-8) M of methalpropalin with detection limits of 1.08 x 10(-9) and 1.87 x 10(-8) M, respectively. The relative SD and correlation coefficients were found to be 1.24%, 0.998 and 1.34%, 0.995, respectively for ten replicates. The method is applied to the determination of the ethalfluralin and methalpropalin in formulations and environmental matrices.

Behaviour and quantification studies of terbacil and lenacil in environmental samples using cyclic and adsorptive stripping voltammetry at hanging mercury drop electrode.

The cyclic voltammograms of terbacil and lenacil at the hanging mercury drop electrode showed a single well defined four electron irreversible peak in universal buffer of pH 4.0 for both compounds. The peak potentials were shifted to more negative values on the increase of pH of the medium, implying the involvement of protons in the electrode reaction and that the proton transfer reaction precedes the proper electrode process. The four electron single peak may be attributed to the simultaneous reduction of carbonyl groups present in 2 and 4 in pyrimidine ring of terbacil and lenacil to the corresponding hydroxy derivative. Based on the interfacial adsorptive character of the terbacil and lenacil onto the mercury electrode surface, a simple sensitive and low cost differential pulse adsorptive stripping voltammetric procedure was optimized for the analysis of terbacil and lenacil. The optimal operational conditions of the proposed procedure were accumulation potential E (acc) = -0.4 V, accumulation time t (acc) = 80 s, scan rate = 40 mV s(-1), pulse amplitude = 25 mV using a universal buffer pH 4.0 as a supporting electrolyte. The linear concentration range was found to be 1.5 x 10(-5) to 1.2 x 10(-9) mol/l and 1.5 x 10(-5) to 2.5 x 10(-8) mol/l with the lower detection limit of 1.22 x 10(-9) and 2.0 x 10(-8) mol/l. The correlation coefficient and relative standard deviation values are found to be 0.942, 0.996, 1.64% and 1.23%, respectively, for 10 replicants. The procedure was successfully applied for determination of terbacil and lenacil in formulations, mixed formulations, environmental samples such as fruit samples and spiked water samples.

Polarographic determination of deltamethrin.

The electrochemical characteristics of deltamethrin have been determined by means of electrochemical techniques such as d.c. polarography, cyclic voltammetry and differential pulse polarography over a wide range of pH from 2.0-12.0. The title compound exhibits a single well defined peak due to the reduction of the CC moiety present in deltamethrin. The overall reduction process is diffusion-controlled and adsorption free in nature. The variation of half-wave potential with the pH, concentration of the title compound, and other experimental conditions is described. A possible mechanism for the reduction is suggested. The number of electrons involved in the electrode reduction is two. Investigation was also undertaken for the determination of deltamethrin in vegetables and in storage bags of rice and wheat under FCI's storage system.

Differential pulse polarographic determination of dicrotophos, crotoxyphos and chlorfenvinphos in grains and soils.

A simple, sensitive and rapid differential pulse polarographic method has been developed for the quantitative determination of organophosphorus pesticides such as dicrotophos, crotoxyphos and chlorfenvinphos in agricultural formulations in universal buffers of a pH range 2.0-12.0. The sample is treated with ethanol to facilitate the dissolution of these pesticides. Both standard addition and calibration methods can be used for the analyses. The lower detection limits are 1.25x10(-9), 1.05x10(-9) and 1.0x10(-9) M, respectively. The method can be applied successfully to determination of these pesticides in grains and soil.