Cutting-edge HPLC and MCR techniques for synchronically quantifying anticholinergic drugs in the presence of C12 and C14 homologs: Robust application to green and white chemistry.

Green and white chemistry are vital to revolutionizing the chemical industry through their unparalleled potential to enhance sustainability and efficiency. In this study, nine sustainability tools of both green and white metrics, including green analytical procedure index (GAPI), ComplexGAPI, analytical greenness, analytical greenness metric for sample preparation, Analytical Eco-Scale (ESA), analytical method greenness score, high-performance liquid chromatography- environmental assessment tool (HPLC-EAT), analytical method volume intensity, and blue applicability grade index (BAGI), have been developed for appraising environmental friendliness for both innovative and straightforward mean centering of ratio spectra (MCR) and reversed-phase high-performance liquid chromatography (RP-HPLC) strategies utilized for concurrent analysis and separation of cyclopentolate (CYC) and C12 and C14 homologs of benzalkonium chloride (BNZ) in pure and ophthalmic solution. The mobile phase, formed of buffer phosphate and acetonitrile (35:65, v/v), was adjusted to pH 6.3, and 215-nm UV detection was used. The experimental flow rate was 2.0 mL min-1, and the analytical column was L11 Inertsil Ph-3 (150 mm × 4.6 mm, 5 µm). All sequences were run at 25°C in the column oven. The MCR approach effectively resolved the drug's spectral overlapping. CYC and BNZ employed this approach at 227.5 and 220.4 nm, respectively. As part of the HPLC analysis, an isocratic method was employed with phosphate buffer and acetonitrile in the mobile phase at 35:65. A correlation coefficient greater than 0.999 was observed between the calibration curves for the HPLC and MCR methods in the ranges of 20-320 µg mL-1 and 5-30 µg mL-1 for all drugs. The technique yields excellent primary recovery rates, ranging from 97.2% to 100.5%. The recommended approach has been validated according to International Council for Harmonization guidelines.

Engineered Microbes for Producing Anticholinergics.

The tropane alkaloids (TAs) hyoscyamine and scopolamine function as acetylcholine receptor antagonists and are used clinically as parasympatholytics to treat neuromuscular disorders in humans. While TAs are synthesized in a small subset of plant families, these specialized metabolites are only accumulated in limited quantities in plant organs. The complex chemical structures of these compounds make their industrial production by chemical synthesis very challenging, Therefore, the supply of these TAs still relies on intensive farming of Duboisia shrubs in tropical countries. Many adverse factors such as climate fluctuations and pandemics can thus influence annual world production. Based on the landmark microbial production of the antimalarial semi-synthetic artemisinin, the Smolke group recently developed a yeast cell factory capable of de novo synthesizing hyoscyamine and scopolamine, thus paving the way for an alternative production of these compounds.

LC-HRMS Profiling and Antidiabetic, Anticholinergic, and Antioxidant Activities of Aerial Parts of Kinkor (Ferulago stellata).

Kinkor (Ferulago stellata) is Turkish medicinal plant species and used in folk medicine against some diseases. As far as we know, the data are not available on the biological activities and chemical composition of this medicinal plant. In this study, the phytochemical composition; some metabolic enzyme inhibition; and antidiabetic, anticholinergic, and antioxidant activities of this plant were assessed. In order to evaluate the antioxidant activity of evaporated ethanolic extract (EEFS) and lyophilized water extract (WEFS) of kinkor (Ferulago stellata), some putative antioxidant methods such as DPPH· scavenging activity, ABTS•+ scavenging activity, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+)-binding activities were separately performed. Furthermore, ascorbic acid, BHT, and α-tocopherol were used as the standard compounds. Additionally, the main phenolic compounds that are responsible for antioxidant abilities of ethanol and water extracts of kinkor (Ferulago stellata) were determined by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Ethanol and water extracts of kinkor (Ferulago stellata) demonstrated effective antioxidant abilities when compared to standards. Moreover, ethanol extract of kinkor (Ferulago stellata) demonstrated IC50 values of 1.772 µg/mL against acetylcholinesterase (AChE), 33.56 ± 2.96 µg/mL against α-glycosidase, and 0.639 µg/mL against α-amylase enzyme respectively.

Metal-Organic Framework with Dual Active Sites in Engineered Mesopores for Bioinspired Synergistic Catalysis.

Here we report the design of an enzyme-inspired metal-organic framework (MOF), 1-OTf-Ir, by installing strong Lewis acid and photoredox sites in engineered mesopores. Al-MOF (1), with mixed 2,2'-bipyridyl-5,5-dicarboxylate (dcbpy) and 1,4-benzenediacrylate (pdac) ligands, was oxidized with ozone and then triflated to generate strongly Lewis acidic Al-OTf sites in the mesopores, followed by the installation of [Ir(ppy)2(dcbpy)]+ (ppy = 2-phenylpyridine) sites to afford 1-OTf-Ir with both Lewis acid and photoredox sites. 1-OTf-Ir effectively catalyzed reductive cross-coupling of N-hydroxyphthalimide esters or aryl bromomethyl ketones with vinyl- or alkynyl-azaarenes to afford new azaarene derivatives. 1-OTf-Ir enabled catalytic synthesis of anticholinergic drugs Pheniramine and Chlorpheniramine.

An insight into medicinal attributes of dithiocarbamates: Bird's eye view.

Dithiocarbamates are considered as an important motif owing to its extensive biological applications in medicinal chemistry. The synthesis of this framework can easily be achieved via a one-pot reaction of primary/secondary amines, CS2, and alkyl halides under catalyst-free conditions or sometimes in the presence of a base. By virtue of its colossal pharmacological scope, it has been an evolving subject of interest for many researchers around the world. The present review aims to highlight various synthetic approaches for dithiocarbamates with the major emphasis on medicinal attributes of these architectures as leads in the drug discovery of small molecules such as HDAC inhibitor, lysine-specific demethylase 1 (LSD1) down-regulator, kinase inhibitor (focal adhesion kinase, pyruvate kinase, Bruton's tyrosine kinase), carbonic anhydrase inhibitor, DNA intercalators, and apoptosis-inducing agents. Moreover, recent medicinal advancements in the synthesis of dithiocarbamate derivatives as anticancer, antifungal, antibacterial, anti-Alzheimer, antitubercular, anti-glaucoma, anti-cholinergic, antihyperglycemic, anti-inflammatory activities have been elaborated with notable examples.

Risk Prediction Method for Anticholinergic Action Using Auto-quantitative Structure-Activity Relationship and Docking Study with Molecular Operating Environment.

Lower urinary tract symptoms (LUTS) induced by anticholinergic drug action impair the QOL of patients and are associated with a poor prognosis. Therefore, it is expedient to develop methods of predicting the anticholinergic side effects of drugs, which we aimed to achieve in this study using a quantitative structure-activity relationship (QSAR) and docking study with molecular operations environment (MOE; Molecular Simulation Informatics Systems [MOLSIS], Inc.) In the QSAR simulation, the QSAR model built using the partial least squares regression (PLS) and genetic algorithm-multiple linear regression (GA-MLR) methods showed remarkable coefficient of determination (R2) and XR2 values. In the docking study, a specific relationship was identified between the adjusted docking score (-S) and bioactivity (pKi) values. In conclusion, the methods developed could be useful for in silico risk assessment of LUTS, and plans are potentially applicable to numerous drugs with anticholinergic activity that induce serious side effects, limiting their use.

Hydroxypropyl ß-cyclodextrin nanohybrid monoliths for use in capillary electrochromatography with UV detection: application to the enantiomeric separation of adrenergic drugs, anticholinergic drugs, antidepressants, azoles, and antihistamine.

Two kinds of hydroxypropyl ß-cyclodextrin nanohybrid monoliths were synthesized and applied in capillary electrochromatography with UV detection. One column was fabricated by concurrently using glycidyl methacrylate-bonded hydroxypropyl ß-cyclodextrin (GMA-HP-ß-CD), sodium 3-mercaptopropanesulphonate, and alkoxysilanes in the "one-pot" process. The other was prepared by free radical polymerization of GMA-HP-ß-CD, vinylmethylcyclosiloxane, ethylene dimethacrylate, and 2-acrylamido-2-methyl propane sulfonic acid. Compared to the former hybrid monolith, the latter one displayed improved enantiomeric separation. For ten adrenergic drugs, six anticholinergic drugs, two antidepressants, six azoles, and one antihistamine enantiomeric separation was obtained on the monolith synthesized by free radical polymerization. Twelve out of twenty-five drugs were baseline-separated. Especially, anisodamine with two chiral centers was successfully separated with resolution values of 3.06, 2.11, and 2.17. The nanohybrid monoliths were characterized by optical microscopy, scanning electron microscopy, FT-IR, nitrogen adsorption analysis, and thermogravimetric analysis. Relative standard deviation values less than 5% were obtained through run-to-run, day-to-day, and column-to-column investigations (n = 3). Graphical abstract Schematic representation of two kinds of hydroxypropyl ß-cyclodextrin nanohybrid monoliths based on "one-pot" approach (route I) and free radical polymerization approach (route II), respectively.

Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials.

Recently, the pyridazine nucleus has been widely studied in the field of particular and new medicinal factors as drugs acting on the cardiovascular system. Additionally, a number of thienopyridazines have been claimed to possess interacting biological macromolecules and pharmacological activities such as NAD(P)H oxidase inhibitor, anticancer, and identified as a novel allosteric modulator of the adenosine A1 receptor. The literature survey demonstrates that coumarin, 1,2-pyrazole benzothiazole, and 1,3- thiazole scaffolds are the most versatile class of molecules. In this study, a series of substituted pyrazole[3,4-d]pyridazine derivatives (2a-n) were prepared, and their structures were characterized by Mass analysis, NMR, and FT-IR. These obtained pyrazole[3,4-d]pyridazine compounds were very good inhibitors of the carbonic anhydrase (hCA I and II) isoenzymes and acetylcholinesterase (AChE) with Ki values in the range of 9.03 ±â€¯3.81-55.42 ±â€¯14.77 nM for hCA I, 18.04 ±â€¯4.55-66.24 ±â€¯19.21 nM for hCA II, and 394.77 ±â€¯68.13-952.93 ±â€¯182.72 nM for AChE, respectively. The possible inhibition mechanism of the best-posed pyrazole[3,4-d]pyridazine and pyrazole-3-carboxylic acid derivatives and their interaction with catalytic active pocket residues were determined based on the calculations.

Synthesis and characterization of novel bromophenols: Determination of their anticholinergic, antidiabetic and antioxidant activities.

In this paper, a series of novel bromophenol derivatives were synthesized and evaluated for their acetylcholinesterase and α-glycosidase enzymes inhibition properties and antioxidant activity. Diarylmethanones were synthesized and their bromination was carried out. During bromination, some compounds gave new bromophenols via regioselective O-demethylation. Demethylation of brominated diarylmethanones was also performed with BBr3 to give novel bromophenols. In addition, we examines the antioxidant capacity of novel bromophenol derivatives using several in vitro bioanalytical methodologies such as 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS⋅+) and 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) radical scavenging activity, Fe3+ and Cu2+ reducing activities and ferrous (Fe2+) ions chelating activities. Also, novel bromophenols and methoxylated bromophenols derivatives were tested against acetylcholinesterase and α-glycosidase, which associated with some metabolic diseases. The novel bromophenols showed Ki values in range of 8.94 ±â€¯0.73-59.45 ±â€¯14.97 nM against AChE and 4.31 ±â€¯1.93-44.14 ±â€¯2.19 nM against α-glycosidase.

Novel eugenol bearing oxypropanolamines: Synthesis, characterization, antibacterial, antidiabetic, and anticholinergic potentials.

Five oxypropanol amine derivatives that four of them are novel have been synthesized with high yields and practical methods. in vitro antibacterial susceptibility of Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus strains to synthesized substances were evaluated with agar well-diffusion method by comparison with commercially available drugs. Most of the bacteria were multidrug resistant. It was concluded that these compounds are much more effective than reference drugs. These eugenol bearing oxypropanolamine derivatives were also effective inhibitors against α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzymes with Ki values in the range of 0.80 ±â€¯0.24-3.52 ±â€¯1.01 µM for hCA I, 1.08 ±â€¯0.15-3.64 ±â€¯0.92 µM for hCA II, 5.18 ±â€¯0.84-12.46 ±â€¯2.08 µM for α-glycosidase, and 11.33 ±â€¯2.83-32.81 ±â€¯9.73 µM for AChE, respectively.

Phytochemical Content, Antidiabetic, Anticholinergic, and Antioxidant Activities of Endemic Lecokia cretica Extracts.

The aim of this work was to investigate the enzyme inhibition, antioxidant activity, and phenolic compounds of Lecokia cretica (Lam.) DC. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase enzymes were strongly inhibited by the L. cretica extracts. IC50 values for the three enzymes were found as 3.21 mg/mL, 2.1 mg/mL, and 2.07 mg/mL, respectively. Antioxidant activities were examined in both aqueous and ethanol (EtOH) extracts using CUPRAC, FRAP, and DPPH method. Also, the phenolic compounds of the endemic plant were identified and quantified by using HPLC/MS/MS. According to the results, the extracts have remarkable antioxidant activities. The most abundant phenolic acids of L. cretica in EtOH extract were determined as quinic acid (12.76 mg/kg of crude extract), chlorogenic acid (3.39 mg/kg), and malic acid (2.38 mg/kg).

Synthesis, crystal structure, and biological evaluation of optically active 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-3-carbonitriles: Antiepileptic, antidiabetic, and anticholinergics potentials.

In the presence of chiral organic catalysts, the optically active 4H-chromine was synthesized from the multicomponent condensation of 5,5-dimethylcyclohexane-1,3-dione with malononitrile and methylene-active compound, and the specific angle of rotation of the compounds was determined in the AUTOPOL-III polarimeter and their structures were confirmed by the X-ray spectroscopic analysis method. These optically active 2-amino-4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-3-carbonitriles were effective inhibitors of α-glycosidase, the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzymes with Ki values in the range of 21.33 ± 1.11 to 40.24 ± 10.78 µM for hCA I, 28.91 ± 6.51 to 59.97 ± 15.62 µM for hCA II, 18.16 ± 3.18 to 66.57 ± 1.36 µM for α-glycosidase, and 8.68 ± 0.93 to 102.61 ± 24.96 µM for AChE.

Aminopyrazole-substituted metallophthalocyanines: Preparation, aggregation behavior, and investigation of metabolic enzymes inhibition properties.

The synthesis, characterization, aggregation behavior, theoretical studies, and investigation of antimicrobial, antidiabetic, and anticholinergic properties of 4-(2-(5-amino-4-(4-bromophenyl)-3-methyl-1H-pyrazol-1-yl)ethoxy)phthalonitrile (2) and its soluble aminopyrazole-substituted peripheral metallo (Mn, Co, and Ni)-phthalocyanine complexes (3-5) are reported for the first time. The synthesized compounds and phthalocyanine complexes were characterized spectroscopically. The new phthalonitrile derivative (2) and its peripheral metallophthalocyanine complexes (3-5) were found to be effective inhibitors of α-glycosidase, acetylcholinesterase (AChE), human carbonic anhydrase I and II isoforms (hCA I and II), and butyrylcholinesterase (BChE) with Ki values in the range of 1.55 ± 0.47 to 10.85 ± 3.43 nM for α-glycosidase, 8.44 ± 0.32 to 21.31 ± 7.91 nM for hCA I, 11.73 ± 2.82 to 31.03 ± 4.81 nM for hCA II, 101.62 ± 26.58 to 326.54 ± 89.67 nM for AChE, and 68.68 ± 11.15 to 109.53 ± 19.55 nM for BChE. This is the first study of peripherally substituted phthalocyanines containing an aminopyrazole group as potential carbonic anhydrase enzyme inhibitor. Also, the antimicrobial activities of the synthesized compounds were evaluated against six microorganisms (four bacteria and two Candida species) using the broth microdilution method. The gram-positive bacteria were detected to be more sensitive than gram-negative bacteria and yeasts in the synthesized compounds.

A convenient synthesis of the muscarinic cholinergic antagonist (R)-[N-methyl-3 H]quinuclidinyl benzilate methiodide.

A useful synthesis of (R)-[N-methyl-3 H]quinuclidinyl benzilate methiodide is described with the product characterized by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), tritium nuclear magnetic resonance (NMR), and mass spectrometry (MS). Several methods are provided to purify the radioligand, and its storage and stability are also discussed.

Molecular Docking Studies of Coumarins Isolated from Extracts and Essential Oils of Zosima absinthifolia Link as Potential Inhibitors for Alzheimer's Disease.

Coumarins and essential oils are the major components of the Apiaceae family and the Zosima genus. The present study reports anticholinesterase and antioxidant activities of extracts and essential oils from aerial parts, roots, flowers, fruits and coumarins-bergapten (1); imperatorin (2), pimpinellin (3) and umbelliferone (4)-isolated of the roots from Zosima absinthifolia. The investigation by light and scanning electron microscopy of the structures of secretory canals found different chemical compositions in the various types of secretory canals which present in the aerial parts, fruits and flowers. The canals, present in the aerial parts, are characterized by terpene hydrocarbons, while the secretory canals of roots, flowers and fruits include esters. Novel data of a comparative study on essential oils constituents of aerial parts, roots, flowers and fruits of Z. absinthfolia has been presented. The roots and fruits extract showed a high content of total phenolics and antioxidant activity. The GC-FID and GC-MS analysis revealed that the main components of the aerial parts, roots, flowers and fruits extracts were octanol (8.8%), octyl octanoate (7.6%), octyl acetate (7.3%); trans-pinocarvyl acetate (26.7%), ß-pinene (8.9%); octyl acetate (19.9%), trans-p-menth-2-en-1-ol (4.6%); octyl acetate (81.6%), and (Z)-4-octenyl acetate (5.1%). The dichloromethane fraction of fruit and flower essential oil was characterized by the highest phenolics level and antioxidant activity. The dichloromethane fraction of fruit had the best inhibition against butyrylcholinesterase enzyme (82.27 ± 1.97%) which was higher then acetylcholinesterase inhibition (61.09 ± 4.46%) of umbelliferone. This study shows that the flowers and fruit of Z. absinthifolia can be a new potential resource of natural antioxidant and anticholinesterase compounds.

Bunias erucago L.: Glucosinolate Profile and In Vitro Biological Potential.

Bunias erucago belongs to the Brassicaceae family, which represents a forgotten crop of the Euro-Mediterranean area. The aim of the present study was to determine the glucosinolate profile in different plant parts and biological properties (antioxidant, anticholinesterase, and cytotoxic activities) of the isolates containing glucosinolate breakdown products. The chemical profiles were determined by using HPLC-PDA-MS/MS of desulfoglucosinolates and GC-MS of glucosinolate degradation products. The analysis of B. erucago showed the presence of seven glucosinolates: gluconapin (1), glucoraphasatin (2), glucoraphenin (3), glucoerucin (4), glucoraphanin (5), glucotropaeolin (6), and glucosinalbin (7). The total glucosinolate content ranged from 7.0 to 14.6 µmol/g of dry weight, with the major glucosinolate glucosinalbin in all parts. The antioxidant activity of all volatile isolates was not notable. At a tested concentration of 227 µg/mL, flower hydro-distillate (FH) showed good AChE inhibition, i.e., 40.9%, while root hydro-distillate (RH) had good activity against BChE, i.e., 54.3%. FH showed the best activity against both tested human bladder cancer cell lines, i.e., against T24 after 72 h, which have IC50 of 16.0 µg/mL, and against TCCSUP after 48 h with IC50 of 7.8 µg/mL, and can be considered as highly active. On the other hand, RH showed weak activity against tested cancer cells.

E3317 promotes cholesterol efflux in macrophage cells via enhancing ABCA1 expression.

Reverse cholesterol transport (RCT) plays an important role in cholesterol and lipid metabolism. Regulating the activities of key transporters and receptors in RCT, such as ATP-binding cassette transporter A1 (ABCA1), helps to prevent atherosclerotic cardiovascular disease. In this study, we used an ABCA1 promoter luciferase reporter assay to screen 20,000 compounds for ABCA1 upregulators. Compound E3317 (N-(6-butylbenzo[d]thiazol-2(3H)-ylidene)-3-(N-(2-cyanoethyl)sulfamoyl)benzamide)) was identified as a positive hit with an EC50 value of 0.2 µM in ABCA1p-LUC HepG2 cells. Thus, we hypothesized that E3317 might have cholesterol- and lipid metabolism-regulating effects through ABCA1 upregulation. E3317 significantly increased ABCA1 mRNA and protein expression in hepatic L02 cells and RAW264.7 macrophages. E3317 promoted cholesterol efflux to apolipoprotein A-I in RAW264.7 macrophages and significantly decreased lipid accumulation in oxidized low-density lipoprotein-induced murine RAW264.7 macrophages. Further studies using ABCA1 siRNA showed that the promotion of cholesterol efflux and decrease of lipid accumulation by E3317 depended on ABCA1 expression. Mechanistic studies indicated that E3317 regulated ABCA1 expression via activating nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays an important role in the regulation of glucose homeostasis and lipid metabolism. The structure of E3317 was docked in the ligand-binding domain of PPARγ (PBD code: 4EMA) to find the key binding amino acids. Site mutation assays confirmed that Y327 and F363 were the key PPARγ binding epitopes of E3317. Our results revealed that E3317 upregulates ABCA1 expression and thereby promotes cholesterol efflux. E3317 may regulate ABCA1 expression through PPARγ. Our findings provide a new compound, E3317, which may have beneficial cardiovascular effects.

Protein Surface Structural Recognition in Inactive Areas: A New Immobilization Strategy for Acetylcholinesterase.

This work reported a new method of design for the immobilization of acetylcholinesterase (AChE) based on its molecular structure to improve its sensitivity and stability. The immobilization binding site on the surface of AChE was determined using MOLCAD's multi-channel functionality. Then, 11 molecules ((+)-catechin, (-)-epicatechin, (-)-gallocatechin, hesperetin, naringenin, quercetin, taxifolin, (-)-epicatechin gallate, flupirtine, atropine, and hyoscyamine) were selected from the ZINC database (about 50 000 molecules) as candidate affinity ligands for AChE. The fluorescence results showed that the binding constant Kb between AChE and the ligands ranged from 0.01344 × 104 to 4.689 × 104 M-1 and there was one independent class of binding site for the ligands on AChE. The AChE-ligand binding free energy ranged from -12.14 to -26.65 kJ mol-1. Naringenin, hesperetin, and quercetin were the three most potent immobilized affinity ligands. In addition, it was confirmed that the binding between the immobilized ligands only occurred at a single site, located in an inactive area on the surface of AChE, and did not affect the enzymatic activity as shown through a competition experiment and enzyme assay. This method based on protein surface structural recognition with high sensitivity and stability can be used as a generic approach for design of the enzyme immobilization and biosensor development.

Study of the enantiomeric separation of the anticholinergic drugs on two immobilized polysaccharide-based chiral stationary phases by HPLC and the possible chiral recognition mechanisms.

In this work, the enantiomeric separation of ten anticholinergic drugs was first examined on two derivative polysaccharide chiral stationary phases (CSPs), i.e., Chiralpak ID and Chiralpak IA in the normal phase mode. Except for scopolamine hydrobromide, the remaining nine analytes could be completely separated with good resolutions using both columns under the optimized mobile phase conditions. And the enantiomeric discrimination ability of the studied CSPs towards nine analytes was in the order of Chiralpak ID > Chiralpak IA. The influences of organic modifier types, alcohol content, and base/acid additives on the enantiomeric separation were evaluated and optimized. According to the experimental results, the effect of the structures of analytes on enantiomeric separation was discussed. Additionally, the chiral recognition mechanisms were proposed based on the thermodynamic analysis of the experimental data.

Synthesis, crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N-salicyloil-N'-maleoil-hydrazine as anticholinergic and antidiabetic agents.

[Ni(C11 H9 N2 O5 )2 (H2 O)2 ]•3(C3 H7 NO) (1) and [Co(C11 H9 N2 O5 )2 (H2 O)2 ]•3(C3 H7 NO) (2) are synthesized and characterized by elemental analysis, FT-IR spectra, magnetic susceptibility, and thermal analysis. In addition, the crystal structure of Ni(II) complex is presented. Both complexes show distorted octahedral geometry. In 1 and 2, metal ions are coordinated by two oxygen atoms of salicylic residue and two nitrogen atoms of maleic amide residue from two ligands, and two oxygen atoms from two water molecules. In this paper, both compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I, and II, α-glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compounds 1 and 2 had Ki values of 18.36 ± 4.38 and 26.61 ± 7.54 nM against hCA I and 13.81 ± 3.02 and 29.56 ± 6.52 nM against hCA II, respectively. On the other hand, their Ki values were found to be 487.45 ± 54.18 and 453.81 ± 118.61 nM against AChE and 199.21 ± 50.35 and 409.41 ± 6.86 nM against BChE, respectively.