Convergent synthesis of carbonic anhydrase inhibiting bi-heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition,kinetics, and computational studies

By using a convergent methodology, a novel series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole–triazole core was synthesized, and the structures of these hybrid molecules, 9a–k , were corroborated through spectral analyses. The in vitro studies of these multifunctional molecules demonstrated their potent carbonic anhydrase inhibition relative to the standard used. The kinetics mechanism was exposed by Lineweaver–Burk plots, which revealed that 9j inhibited carbonic anhydrase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants K_i calculated from Dixon plots for this compound was 1.2 μM. The computational study was also persuasive with the experimental results, and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to carbonic anhydrase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for various diseases related to the uncontrolled production of this enzyme.     

Structural,Magnetic and Catalytic Properties of a New Vacancy Ordered Perovskite Type Barium Cobaltate BaCoO2.67

A new vacancy ordered, anion deficient perovskite modification with composition of BaCoO_2.67 (Ba₃Co₃O₈□₁) has been prepared via a two-step heating process. Combined Rietveld analysis of neutron and X-ray powder diffraction data shows a novel ordering of oxygen vacancies not known before for barium cobaltates. A combination of neutron powder diffraction, magnetic measurements, and density functional theory (DFT) studies confirms G-type antiferromagnetic ordering. From impedance measurements, the electronic conductivity of the order of 10⁻⁴ S cm⁻¹ is determined. Remarkably, the bifunctional catalytic activity for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is found to be comparable to that of Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3–y, confirming that charge-ordered anion deficient non-cubic perovskites can be highly efficient catalysts.     

Solving mixed-integer robust optimization problems with interval uncertainty using Benders decomposition

Uncertainty and integer variables often exist together in economics and engineering design problems. The goal of robust optimization problems is to find an optimal solution that has acceptable sensitivity with respect to uncertain factors. Including integer variables with or without uncertainty can lead to formulations that are computationally expensive to solve. Previous approaches for robust optimization problems under interval uncertainty involve nested optimization or are not applicable to mixed-integer problems where the objective or constraint functions are neither quadratic, nor linear. The overall objective in this paper is to present an efficient robust optimization method that does not contain nested optimization and is applicable to mixed-integer problems with quasiconvex constraints (? type) and convex objective funtion. The proposed method is applied to a variety of numerical examples to test its applicability and numerical evidence is provided for convergence in general as well as some theoretical results for problems with linear constraints.     

Stability-Indicating Densitometric High-Performance Thin-Layer Chromatographic Method for the Quantitative Analysis of Biomarker Naringin in the Leaves and Stems of Rumex vesicarius L.

JPC – Journal of Planar Chromatography – Modern TLC - A simple, sensitive, and stability-indicating high-performance thinlayer chromatography (HPTLC)-densitometric method was developed...     

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant,Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H₂O₂) were found to be IC₅₀ = 66.16 μg/mL and 76.05 μg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC₅₀ = 64.91 μg/mL) and Caco-2 (IC₅₀ = 83.98 μg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.     

Evaluating the mobility of toxic metals in untreated industrial wastewater sludge using a BCR sequential extraction procedure and a leaching test

The distribution and speciation of toxic metals in industrial wastewater sludge (IWS) was investigated. In this work, the modified BCR three-stage sequential extraction procedure was applied to the fractionation of Cr Pb Ni, and Cd in untreated industrial wastewater sludge from industrial sites in Hyderabad (Pakistan). The extracts were analyzed using electrothermal atomic absorption spectrometry. The procedure was evaluated using a certified reference material for soil mixed with sewage sludge BCR 483. The results from the partitioning study indicate that more easily mobilized forms (acid exchangeable) of Cd were dominant. The oxidizable fraction was dominant for all four toxic metals. Metal recovery was good, with <4% difference between the total metal recovered through the extractant steps and the total metal determined after microwave digestion. Lixiviation tests (DIN 38414-S4) were used to evaluate the leaching of toxic species from IWS, and it was observed that levels of leachable toxic metals were low compared to the amount of metal extracted in the exchangeable fraction of the BCR protocol.     

Development and validation of HPLC method for simultaneous estimation of piperine and guggulsterones in compound Unani formulation (tablets) and a nanoreservoir system

An attempt has been made to develop and validate a simultaneous HPLC method for novel approach of drug release via oil‐in‐water (o/w) nanoemulsion formulation and Habb‐e‐Khardal Unani tablet containing piperine and guggul sterones E and Z as main ingredients. Nanoemulsion was prepared by titration method using sefsol‐218 as an oily phase, cremophor‐EL as a surfactant, transcutol as a co‐surfactant and distilled water as an aqueous phase. The formulation was optimized on the basis of thermodynamic stability and dispersibilty test. The nanoformulation was evaluated for particle size, surface morphology, electrical conductivity and viscosity determination. The in vitro dissolution was carried out by dialysis bag method. Drugs were quantified using an HPLC method developed in‐house with a C₁₈ column as stationary phase and acetonitrile and water as mobile phase at λ_max of 240 nm. The optimized formulation showed higher drug release, lower droplet size and less viscosity as compared with the conventional Habb‐e‐Khardal Unani tablet. The present study illustrated the potential of nanoemulsion dosage form in improving biopharmaceutic performance of piperine and guggul sterone. The HPLC method was also found to be quite sufficient for the routine quality control of formulations containing piperine and guggul sterone E and Z as ingredients and also for in vitro drug release studies. Copyright © 2011 John Wiley & Sons, Ltd.     

Stereoselective synthesis of beta-substituted phenylalanine-beta-phenylisoserine-derived tripeptides using N-cinnamoyl-L-proline as template: synthesis of structural analogues of HIV protease inhibitors

N-Cinnamoyl-L-proline can be used as a template on which beta-substituted phenylalanine and beta-phenylisoserine residues can be synthesized leading to tripeptide derivatives as structural analogues of HIV protease inhibitors.