The first synthesis,carbonic anhydrase inhibition and anticholinergic activities of some bromophenol derivatives with S including natural products

Starting from vanillin, known four benzyl bromides with Br were synthesized. The first synthesis of natural product 3,4-dibromo-5-((methylsulfonyl)methyl)benzene-1,2-diol (2) and 3,4,6-tribromo-5-((methylsulfonyl)methyl)benzene-1,2-diol (3) and derivatives were carried out by demethylation, acetylatilation, oxidation and hydrolysis reactions of the benzyl bromides. Also, these compounds were tested against some important enzymes like acetylcholinesterase and butyrylcholinesterase enzymes, carbonic anhydrase I, and II isoenzymes. The novel bromophenols showed Ki values of in range of 53.75 ± 12.54–234.68 ± 46.76 nM against hCA I, 42.84 ± 9.36 and 200.54 ± 57.25 nM against hCA II, 0.84 ± 0.12–14.63 ± 3.06 nM against AChE and 0.93 ± 0.20–18.53 ± 5.06 nM against BChE. Induced fit docking process performed on the compounds inhibiting hCA I, hCA II, AChE, and BChE receptors. Hydroxyl group should exist at the aromatic ring of the compounds for inhibition of the enzymes. The moieties reported in this study will be useful for design of more potent and selective inhibitors against the enzymes.     

Synthesis,characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes

In this study, a series of novel bis-thiomethylcyclohexanone compounds (3a–3j) were synthesized by the addition of thio-Michael to the bis-chalcones under mild reaction conditions. The bis-thiomethylcyclohexanone derivatives (bis-sulfides) were characterized by ¹H NMR, ¹³C NMR, FTIR and elemental analysis techniques. Furthermore, the molecular and crystal structures of 3h, 3i and 3j compounds were determined by single crystal X-ray diffraction studies. In this study, X-ray crystallography provided an alternative and often-complementary means for elucidating functional groups at the enzyme inhibitory site. Acetylcholinesterase (AChE) is a member of the hydrolase protein super family and has a significant role in acetylcholine-mediated neurotransmission. Here, we report the synthesis and determining of novel bis-thiomethylcyclohexanone compounds based hybrid scaffold of AChE inhibitors. The newly synthesized bis-thiomethylcyclohexanone compounds showed K_i values of in range of 39.14–183.23 nM against human carbonic anhydrase I isoenzyme (hCA I), 46.03–194.02 nM against human carbonic anhydrase II isoenzyme (hCA II), 4.55–32.64 nM against AChE and 12.77–37.38 nM against butyrylcholinesterase (BChE). As a result, novel bis-thiomethylcyclohexanone compounds can have promising anti Alzheimer drug potential and record novel hCA I, and hCA II enzymes inhibitor.     

Synthesis of some tetrahydropyrimidine-5-carboxylates,determination of their metal chelating effects and inhibition profiles against acetylcholinesterase,butyrylcholinesterase and carbonic anhydrase

2-(Methacryloyloxy)ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate, is a cyclic urea derivative synthesized from urea, 2-(methacryloyloxy) ethyl acetoacetate and substituted benzaldehyde, and tested in terms of the inhibition of two physiologically relevant carbonic anhydrase (CA) isozymes I and II. Acetylcholinesterase (AChE) is found in high concentrations in the red blood cells and brain. Butyrylcholinesterase (BChE) is another enzyme abundantly present in the liver and released into blood in a soluble form. Also, they were tested for the inhibition of AChE and BChE enzymes and demonstrated effective inhibition profiles with Ki values in the range of 429.24–530.80?nM against hCA I, 391.86–530.80?nM against hCA II, 68.48–97.19?nM against AChE and 104.70–214.15?nM against BChE. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 281.33?nM against hCA I, and 202.70?nM against hCA II. Also, Tacrine inhibited AChE and BChE showed Ki values of 396.03 and 209.21?nM, respectively.     

The inhibitory effects of phenolic Mannich bases on carbonic anhydrase I and II isoenzymes

Phenolic mono Mannich bases [2-[4-hydroxy-3-(aminomethyl)benzylidene]-2,3-dihydro-1H-inden-1-one (8–15)] and bis Mannich bases [2-[4-hydroxy-3,5-bis(aminomethyl)benzylidene]-2, 3-dihydro-1H-inden-1-one (2–7)] were synthesized starting from 2-(4-hydroxybenzylidene)-2, 3-dihydro-inden-1-one (1). This study was designed in order to investigate the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties of a library of compounds incorporating the phenol functional group. All prepared compounds showed a low inhibition percentages on both human (h) isoforms hCA I and hCA II compared to the reference sulfonamide acetazolamide. Mannich bases 2–15 had lower inhibition percentages than the compound 1 on hCA I and hCA II, except compound 14, which is a Mannich base derivative of dipropylamine, which had a similar inhibitory power as compound 1 on hCA II. All compounds synthesized 1–15 were 1.3–1.9 times more effective on hCA II comparing with the effectivenes of the compounds on hCA I.     

The impact of some natural phenolic compounds on carbonic anhydrase,acetylcholinesterase, butyrylcholinesterase,and α‐glycosidase enzymes: An antidiabetic,anticholinergic, and antiepileptic study

Natural products from food and plant sources have been used for medicinal usage for ages. Also, natural products with therapeutic significance are compounds derived from animals, plants, or any microorganism. In this study, chrysin, carvacrol, hesperidin, zingerone, and naringin as natural phenols showed excellent inhibitory effects against human (h) carbonic anhydrase (CA) isoforms I and II (hCA I and II), α‐glucosidase (α‐Gly), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). These phenolic compounds were tested for the inhibition of α‐glycosidase, hCA I, hCA II, AChE, and BChE enzymes and demonstrated efficient inhibition profiles with K_i values in the range of 3.70 ± 0.92–79.66 ± 20.81 nM against hCA I, 2.98 ± 0.33–84.88 ± 40.32 nM against hCA II, 4.93 ± 2.01–593.60 ± 134.74 nM against α‐Gly, 0.52 ± 0.18–46.80 ± 17.15 nM against AChE, and 1.25 ± 0.22–32.08 ± 2.68 against BChE.     

Synthesis and bioactivity of several new hetaryl sulfonamides

1-(4-Methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles were synthesized from different tetrahydropyrimidinethiones and aryl sulfonyl chloride. These compunds were tested for metal chelating effects and to determine the phrase in which inhibition occured between two physiologically pertinent compunds and carbonic anhydrase (CA) isozymes I and II (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). AChE was detected in high concentrations in the brain and red blood cells. BChE is another enzymes that is abundant available in the liver and released into the blood in a soluble form. Newly synthesized hetaryl sulfonamides exhibited impressive inhibition profiles with Ki values in the range of 1.42–6.58?nM against hCA I, 1.72–7.41?nM against hCA II, 0.20–1.14?nM against AChE and 1.55–5.92?nM against BChE. Moreover, acetazolamide showed Ki values of 43.69?±?6.44?nM against hCA I and 31.67?±?8.39?nM against hCA II. Additionally, tacrine showed Ki values of 25.75?±?3.39?nM and 37.82?±?2.08 against AChE and BChE, respectively.     

Synthesis,Spectroscopic Analysis,and in Vitro/in Silico Biological Studies of Novel Piperidine Derivatives Heterocyclic Schiff-Mannich Base Compounds

In the present study, 3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( S1-8 ) were synthesized by treating 4-hydroxybenzaldehyde ( B ) with eight different 3-substitued-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones ( T1-8 ) in acetic acid medium, separately. The synthesized Schiff bases ( S ) were reacted with formaldehyde and secondary amine such as 4-piperidinecarboxyamide to afford novel heterocyclic bases. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( T ) were treated with 4-piperidinecarboxyamide in the presence of formaldehyde to synthesize eight new 1-(4-piperidinecarboxyamide-1-yl - methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones ( M1-8 ). The structure characterization of compounds was carried out using ¹H-NMR, IR, HR-MS, and ¹³C-NMR spectroscopic methods. The inhibitory properties of the newly synthesized compounds were calculated against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes. Ki values were calculated in the range of 20.06±3.11–36.86±6.17 μM for GST, 17.87±2.91–30.53±4.25 μM for AChE, 9.08±0.69–20.02±2.88 μM for BChE, respectively, Besides, IC₅₀ values were also calculated. Best binding scores of -inhibitors against used enzymes were calculated as −12.095 kcal/mol, −12.775 kcal/mol, and −9.336 kcal/mol, respectively. While 5-oxo-triazole piperidine-4-carboxamide moieties have a critical role in the inhibition of AChE and GST enzymes, hydroxy benzyl moiety is important for BChE enzyme inhibition.     

Synthesis of novel bis‐sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase,acetylcholinesterase, and butyrylcholinesterase

In this study, a series of novel bis‐sulfone compounds ( 2a‐2j ) were synthesized by oxidation of the bis‐sulfides under mild reaction conditions. The bis‐sulfone derivatives were characterized by ¹H‐NMR, ¹³C‐NMR, Fourier‐transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis‐sulfone derivatives. Here, we report the synthesis and testing of novel bis‐sulfone compound–based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward the therapy of Alzheimer's disease. The novel synthesized bis‐sulfone compounds demonstrated K_i values between 11.4 ± 3.4 and 70.7 ± 23.2 nM on human carbonic anhydrase I isozyme (hCA I), 28.7 ± 6.6 to 77.6 ± 5.6 nM on human carbonic anhydrase II isozyme (hCA II), 18.7 ± 2.61 to 95.4 ± 25.52 nM on AChE, and 9.5 ± 2.1 to 95.5 ± 1.2 nM on BChE enzymes. The results showed that novel bis‐sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.     

Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis,characterization, acetylcholinesterase,butyrylcholinesterase, and carbonic anhydrase inhibitory properties

The thiolation reaction was carried out in a benzene solution at 80°C and p‐substituted ketones and mercaptoacetic acid in a molar ratio (1:4) of in the presence of a catalytic amount of toluene sulfonic acids. The enzyme inhibition activities of the novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives were investigated. These novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives showed good inhibitory action against acetylcholinesterase (AChE) butyrylcholinesterase (BChE), and human carbonic anhydrase I and II isoforms (hCA I and II). AChE inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. Many clinically established drugs are carbonic anhydrase inhibitors, and it is highly anticipated that many more will eventually find their way into the market. The novel synthesized compounds inhibited AChE and BChE with K_i values in the range of 0.64–1.47 nM and 9.11–48.12 nM, respectively. On the other hand, hCA I and II were effectively inhibited by these compounds, with K_i values between 63.27–132.34 and of 29.63–127.31 nM, respectively.     

Synephrine and phenylephrine act as α‐amylase, α‐glycosidase,acetylcholinesterase, butyrylcholinesterase,and carbonic anhydrase enzymes inhibitors

In this paper, synephrine and phenylephrine compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I and II, α‐amylase, α‐glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Synephrine and phenylephrine had K_i values of 199.02 ± 16.01 and 65.01 ± 5.00 μM against hCA I and 336.02 ± 74.01 and 92.04  ±  18.03 μM against hCA II, respectively. On the other hand, their K_i values were found to be 169.10  ±  80.03 and 88.03  ±  5.01 nM against AChE and 177.06  ±  6.01 and 78.03  ±  3.05 nM against BChE, respectively. α‐Amylase and α‐glycosidase enzymes were easily inhibited by these compounds. α‐Glycosidase inhibitors, generally defined to as starch blockers, are anti‐diabetic drugs that help to decrease post comestible blood glucose levels.     

Discovery of potent carbonic anhydrase,acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine‐4‐ones synthesized on an acetophenone base

Compounds containing nitrogen and sulfur atoms can be widely used in various fields, including industry, medicine, biotechnology, and chemical technology. Among them, amides of acids and heterocyclic compounds have an important place. These amides and thiazolidine‐4‐ones showed good inhibitory action against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoforms. AChE exists at high concentrations in the brain and red blood cells. BChE is an important enzyme that is plentiful in the liver, and it is released into the blood in a soluble form. They were demonstrated to have effective inhibition profiles with K_i values of 23.76–102.75 nM against hCA I, 58.92–136.64 nM against hCA II, 1.40–12.86 nM against AChE, and 9.82–52.77 nM against BChE. On the other hand, acetazolamide showed K_i value of 482.63 ± 56.20 nM against hCA I, and 1019.60 ± 163.70 nM against hCA II. Additionally, Tacrine inhibited AChE and BChE, showing K_i values of 397.03 ± 31.66 and 210.21 ± 15.98 nM, respectively.     

Synthesis and biological evaluation of aminomethyl and alkoxymethyl derivatives as carbonic anhydrase,acetylcholinesterase and butyrylcholinesterase inhibitors

Compounds containing nitrogen and sulfur atoms can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. Therefore, the reactions of aminomethylation and alkoxymethylation of mercaptobenzothiazole, mercaptobenzoxazole and 2-aminothiazole were developed. Additionally, the alkoxymethyl derivatives of mercaptobenzoxazole and 2-aminothiazole were synthesized by a reaction with hemiformals, which are prepared by the reaction of alcohols and formaldehyde. In this study, the inhibitory effects of these molecules were investigated against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) enzymes and carbonic anhydrase I, and II isoenzymes (hCA I and II). Both hCA isoenzymes were significantly inhibited by the recently synthesized molecules, with K_i values in the range of 58–157?nM for hCA I, and 81–215?nM for hCA II. Additionally, the K_i parameters of these molecules for BChE and AChE were calculated in the ranges 23–88 and 18–78?nM, respectively.     

Synthesis and discovery of potent carbonic anhydrase,acetylcholinesterase, butyrylcholinesterase,and α‐glycosidase enzymes inhibitors: The novel N,N′‐bis‐cyanomethylamine and alkoxymethylamine derivatives

During this investigation, N,N′‐bis‐azidomethylamines, N,N′‐bis‐cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N‐bis‐cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α‐glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K_i values in the range of 0.15–13.31 nM for α‐glycosidase, 2.77–15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12–21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33–73.23 nM for AChE, and 3.84–48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances.     

The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase,acetylcholinesterase and butyrylcholinesterase enzymes

The first synthesis of (E)-4-(3-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (1), (E)-4-(2-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (2), and (E)-4-(2,3-dibromo-4,5-dihydroxyphenyl)but-3-en-2-one (3) was realized as natural bromophenols. Derivatives with mono OMe of 2 and 3 were obtained from the reactions of their derivatives with di OMe with AlCl₃. These novel 4-phenylbutenone derivatives were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with K_i values in the range of 158.07–404.16 pM for hCA I, 107.63–237.40 pM for hCA II, 14.81–33.99 pM for AChE and 5.64–19.30 pM for BChE. The inhibitory effects of the synthesized novel 4-phenylbutenone derivatives were compared to acetazolamide as a clinical hCA I and II isoenzymes inhibitor and tacrine as a clinical AChE and BChE enzymes inhibitor.     

Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma,Alzheimer's Disease and Diabetes Mellitus

Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85–94 %) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (¹H-NMR, ¹³C-NMR), and High-Resolution Mass Spectroscopy (HR-MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the K_i values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α-Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.     

Vinyl functionalized 5,6-dimethylbenzimidazolium salts: Synthesis and biological activities

A series of vinyl functionalized 5,6-dimethylbenzimidazolium salts are synthesized. All compounds were fully characterized by elemental analyses, MS, ¹H-NMR, ¹³C-NMR, and IR spectroscopy techniques. Enzyme inhibition is a very active area of research in drug design and development. In this study, the synthesized novel benzimidazolium salts were evaluated toward the human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. They demonstrated highly potent inhibition ability against hCA I with K_i values of 484.8 ± 62.6–1389.7 ± 243.2 nM, hCA II with K_i values of 298.9 ± 55.7–926.1 ± 330.0 nM, α-glycosidase with K_i values of 170.3 ± 27–760.1 ± 269 μM, AChE with K_i values of 27.1 ± 3–77.6 ± 1.7 nM, and BChE with K_i values of 21.0 ± 5–61.3 ± 15 nM. As a result, novel vinyl functionalized 5,6-dimethylbenzimidazolium salts (1a–g) exhibited effective inhibition profiles toward studied metabolic enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly to treat some global disorders including glaucoma, Alzheimer's disease, and diabetes.     

Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases

Abstract

Phenolic bis Mannich bases having the chemical structure of 1-[3,5-bis-aminomethyl-4-hydroxyphenyl]-3-(4-halogenophenyl)-2-propen-1-ones (1a-c, 2a-c, 3a-c) were synthesized (Numbers 1, 2, and 3 represent fluorine, chlorine, and bromine bearing compounds, respectively, while a, b, and c letters represent the compounds having piperidine, morpholine, and N-methyl piperazine) and their cytotoxic and carbonic anhydrase (CA, EC 4.2.1.1) enzyme inhibitory effects were evaluated. Lead compounds should possess both marked cytotoxic potencies and selective toxicity for tumors. To reflect this potency, PSE values of the compounds were calculated. According to PSE values, the compounds 2b and 3b may serve as lead molecules for further anticancer drug candidate developments. Although the compounds showed a low inhibition potency toward hCA I (25–43%) and hCA II (6–25%) isoforms at 10?μM concentration of inhibitor, the compounds were more selective (1.5–5.2 times) toward hCA I isoenzyme. It seems that the compounds need molecular modifications for the development of better CA inhibitors.     

Design,synthesis and evaluation of new thiazole-piperazines as acetylcholinesterase inhibitors

In this study, some new 2-(4-substituted piperazine-1-yl)-N-[4-(2-methylthiazol-4-yl)phenyl]acetamide derivatives were synthesized. The synthesized compounds were screened for their anticholinesterase activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes by in vitro Ellman’s method. The structural elucidation of the compounds was performed by using IR, ¹H-NMR, ¹³C-NMR and FAB⁺-MS spectral data and elemental analyses results. Biological assays revealed that at 0.1 µM concentration, the most active compounds against AChE were 5n, 5o and 5p that indicated 96.44, 99.83 and 89.70% inhibition rates, respectively. Besides, IC₅₀ value of the compound 5o was determined as 0.011 µM, whereas IC₅₀ value of standard drug donepezil was 0.054 µM. The synthesized compounds did not show any notable inhibitory activity against BChE.     

The synthesis of novel sulfamides derived from β-benzylphenethylamines as acetylcholinesterase,butyrylcholinesterase and carbonic anhydrase enzymes inhibitors

In this study, a series of novel β-benzylphenethylamines and their sulfamide derivatives were synthesized starting from (Z)-2,3-diphenylacrylonitriles. Pd-C catalysed hydrogenation of diphenylacrylonitriles, reduction of propanenitriles with LiAlH₄ in the presence of AlCl₃ followed by addition of conc. HCl afforded β-benzylphenethylamine hydrochloride salts. The reactions of these amine hydrochloride salts with chlorosulfonyl isocyanate (CSI) in the presence of tert-BuOH and excess Et₃N gave sulfamoylcarbamates. Removing of Boc group from the synthesized sulfamoylcarbamates with trifluoroacetic acid (TFA) yielded novel sulfamides in good yields. These novel sulfamides derived from β-benzylphenethylamines were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with K_i values in the range of 0.278–2.260 nM for hCA I, 0.187–1.478 nM for hCA II, 0.127–2.452 nM for AChE and 0.494–1.790 nM for BChE. The inhibitory effects of the synthesized novel sulfamides derived from β-benzylphenethylamines were compared to those of acetazolamide and dorzolamide as clinical hCA I and II isoenzymes inhibitors and tacrine as a clinical AChE and BChE enzymes inhibitors. In addition to in vitro tests, molecular modeling approaches are implemented not only for prediction of the binding affinities of the compounds but also to study their inhibition mechanisms in atomic level at the catalytic domains.     

Comprehensive Phytochemical Content by LC/MS/MS and Anticholinergic,Antiglaucoma, Antiepilepsy,and Antioxidant Activity of Apilarnil (Drone Larvae)

Apilarnil is 3–7 days old drone larvae. It is an organic bee product known to be rich in protein. In this study, the biological activities of Apilarnil were determined by its antioxidant and enzyme inhibition effects. Antioxidant activities were determined by Fe³⁺, Cu²⁺, Fe³⁺-TPTZ ((2,4,6-tris(2-pyridyl)-s-triazine), reducing ability and 1,1-diphenyl-2-picrylhydrazyl (DPPH⋅) scavenging assays. Also, its enzyme inhibition effects were tested against carbonic anhydrase I and II isoenzymes (hCA I, hCA II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Antioxidant activity of Apilarnil was generally lower than the standard molecules in the applied methods. In DPPH⋅ radical scavenging assay, Apilarnil exhibited higher radical scavenging than some standards. Enzyme inhibition results towards hCA I (IC₅₀: 14.2 μg/mL), hCA II: (IC₅₀: 11.5 μg/mL), AChE (IC₅₀: 22.1 μg/mL), BChE (IC₅₀: 16.1 μg/mL) were calculated. In addition, the quantity of 53 different phytochemical compounds of Apilarnil was determined by a validated method by LC/MS/MS. Compounds with the highest concentrations (mg analyte/g dry extract) were determined as quinic acid (1091.045), fumaric acid (48.714), aconitic acid (47.218), kaempferol (39.946), and quercetin (27.508). As a result, it was determined that Apilarnil had effective antioxidant profile when compared to standard antioxidants.