LC-HRMS Profiling and Phenolic Content, Cholinesterase, and Antioxidant Activities of Terminalia citrina.

Terminalia citrina (T. citrina) belongs to the Combretaceae family and is included in the class of medicinal plants in tropical countries such as Bangladesh, Myanmar, and India. The antioxidant activities of lyophilized water (WTE) and alcohol extracts (ETE) of T. citrina fruits, their phenolic content by LC-HRMS, and their effects on cholinesterases (ChEs; AChE, acetylcholinesterase, and BChE, butyrylcholinesterase) were investigated. Especially ten different analytical methods were applied to determine the antioxidant capacity. Compared with similar studies for natural products in the literature, it was determined that both WTE and ETE exhibited strong antioxidant capacity. Syringe and ellagic acids were higher than other acids in ETE and WTE. IC50 values for ETE and WTE in DPPH radical and ABTS⋅+ scavenging activities were calculated as 1.69-1.68 µg mL-1 and 6.79-5.78 µg mL-1 , respectively. The results of the biological investigations showed that ETE and WTE had an inhibition effect against ChEs, with IC50 values of 94.87 and 130.90 mg mL-1 for AChE and 262.55 and 279.70 mg mL-1 for BChE, respectively. These findings indicate that with the prominence of herbal treatments, T. citrina plant may guide the literature in treating Alzheimer's Disease, preventing oxidative damage, and mitochondrial dysfunction.

Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin.

Taxifolin, also known as dihydroquercetin, is a flavonoid commonly found in plants. Carbonic anhydrase (CA, EC 4.2.1.1) plays an important role in many critical physiological events including carbon dioxide (CO2)/bicarbonate (HCO3(-)) respiration and pH regulation. There are 16 known CA isoforms in humans, of which human hCA isoenzymes I and II (hCA I and II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of taxifolin against the slow cytosolic isoenzyme hCA I, and the ubiquitous and dominant rapid cytosolic isoenzyme hCA II were studied. Taxifolin, as a naturally bioactive flavonoid, has a K(i) of 29.2 nM against hCA I, and 24.2 nM against hCA II. For acetylcholinesterase enzyme (AChE) inhibition, K(i) parameter of taxifolin was determined to be 16.7 nM. These results clearly show that taxifolin inhibited both CA isoenzymes and AChE at the nM levels.

Antioxidant, antiradical, and anticholinergic properties of cynarin purified from the Illyrian thistle (Onopordum illyricum L.).

Cynarin is a derivative of hydroxycinnamic acid and it has biologically active functional groups constituent of some plants and food. We elucidated the antioxidant activity of cynarin by using different in vitro condition bioanalytical antioxidant assays like DMPD(•+), ABTS(•+), O2(•-), DPPH(•) and H2O2 scavenging effects, the total antioxidant influence, reducing capabilities, Fe(2+) chelating and anticholinergic activities. Cynarin demonstrated 87.72% inhibition of linoleic acid lipid peroxidation at 30 µg/mL concentration. Conversely, some standard antioxidants like trolox, α-tocopherol, butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) exhibited inhibitions of 90.32, 75.26, 97.61, 87.30%, and opponent peroxidation of linoleic acid emulsion at the identical concentration, seriatim. Also, cynarin exhibited effective DMPD(•+), ABTS(•+), O2(•-), DPPH(•), and H2O2 scavenging effects, reducing capabilities and Fe(2+) chelating effects. On the contrary, IC50 and K(i) parameters of cynarin for acetylcholinesterase enzyme inhibition were determined as 243.67 nM (r(2): 0.9444) and 39.34 ± 13.88 nM, respectively. This study clearly showed that cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities.

9,10-Dibromo-N-aryl-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-diones: Synthesis and Investigation of Their Effects on Carbonic Anhydrase Isozymes I, II, IX, and XII.

N-substituted maleimides were synthesized from maleic anhydride and primary amines. 1,4-Dibromo-dibenzo[e,h]bicyclo-[2,2,2]octane-2,3-dicarboximide derivatives (4a-f) were prepared by the [4+2] cycloaddition reaction of dibromoanthracenes with the N-substituted maleimide derivatives. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the new derivatives were assayed against the human (h) isozymes hCA I, II, IX, and XII. All tested bicyclo dicarboximide derivatives exhibited excellent inhibitory effects in the nanomolar range, with Ki values in the range of 117.73-232.87 nM against hCA I and of 69.74-111.51 nM against hCA II, whereas they were low micromolar inhibitors against hCA IX and XII.

N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II.

Sulfonamides represent a significant class of biologically active compounds that inhibit carbonic anhydrase (CA, EC.: 4.2.1.1) isoenzymes involved in different pathological and physiological events. Sulfonamide CA inhibitors are used therapeutically as diuretic, antiglaucoma, antiobesity and anticancer agents. A series of new sulfonamides were synthesized using imides and tosyl chloride as starting materials. These N-acylsulfonamides efficiently inhibited the cytosolic human carbonic anhydrase isoenzymes I, and II (hCA I, and II), with nanomolar range inhibition constants ranging between 36.4 ± 6.0-254.6 ± 18.0 and 58.3 ± 0.6-273.3 ± 2.5 nM, respectively.

Novel sulphamides and sulphonamides incorporating the tetralin scaffold as carbonic anhydrase and acetylcholine esterase inhibitors.

Reactions of amino, aminomethyl tetralins and benzyl alcohol with chlorosulphonyl isocyanate (CSI) afforded sulphamoyl carbamates. The sulphamoyl carbamates were converted to sulphamides by palladium-catalysed hydrogenolysis. Sulphonamides were synthesized from the reactions of amines with MeSO2 Cl. Inhibition of human (h) carbonic anhydrase (CA) isoenzymes (hCA I, hCA II) and acetylcholine esterase (AChE) was investigated with the synthesized compounds. hCA I and hCA II were inhibited in the low micromolar or sub-micromolar range. The Ki values were in the range of 0.91-9.56 µM against hCA I and of 3.70-27.88 µM against hCA II. Sulphamides 11-13 and sulphonamides 14-16 had moderate inhibition capacity toward AChE. These findings suggest the novel sulphamides 11-13 and sulphonamides 14-16 as AChE and CA isoenzyme inhibitory agents.

COVID-19 pneumonia in patients with impaired fasting glucose, newly diagnosed diabetes and pre-existing diabetes: a tertiary center experience.

COVID-19 infection is known to increase mortality in patients with diabetes. We aim to demonstrate the differences in disease course and clinical outcomes of patients with COVID-19 regarding the presence of impaired fasting glucose, pre-existing diabetes mellitus (DM) or new-onset DM. 236 patients with positive reverse transcription-PCR tests for SARS-CoV-2 were included in this single-center, retrospective observational study between March 2020 and May 2021. Laboratory results, comorbidities, medications and imaging findings were noted. Logistic regression was used to estimate associated factors for admission to the intensive care unit (ICU). 43 patients with normal glucose, 53 with impaired fasting glucose, 60 with newly diagnosed DM, and 80 with pre-existing DM were classified. Patients with pre-existing DM had higher fasting glucose and glycated hemoglobin than the other groups (p<0.001 for all). Patients with newly diagnosed DM were more likely to need dexamethasone 6 mg (p=0.001). In both newly diagnosed diabetes and impaired fasting glucose groups, 250 mg methylprednisolone was needed at higher rates (p=0.002). Newly diagnosed DM had higher rates of intubation (21.6%) and more mortality (20.0%) (p=0.045 and p=0.028, respectively). Mortality and hospitalization in the ICU were lower in the group receiving antidiabetic treatment. The risk of ICU attendance was higher in patients with impaired fasting glucose (HR=1.71, 95% CI: 0.48 to 6.08) and newly diagnosed DM (HR=1.88, 95% CI: 0.57 to 6.17), compared with pre-existing DM and non-diabetics. Newly diagnosed DM and impaired fasting glucose are associated with increased mortality and intubation in inpatients with COVID-19.

Antidiabetic, anticholinergic and antioxidant activities of aerial parts of shaggy bindweed (Convulvulus betonicifolia Miller subsp.) - profiling of phenolic compounds by LC-HRMS.

In order to evaluate the antioxidant activity of evaporated ethanolic extract (EESB) and lyophilized water extract (WESB) of Shaggy bindweed (Convulvulus betonicifolia Mill. Subs), some putative antioxidant methods such as DPPH· scavenging activity, ABTS•+ scavenging effect, ferric ions (Fe3+) reduction method, cupric ions (Cu2+) reducing capacity, and ferrous ions (Fe2+) binding activities were separately performed. Also, ascorbic acid, α-tocopherol and BHT were used as the standard compounds. Additionally, some phenolic compounds that responsible for antioxidant abilities of EESB and WESB were screened by liquid chromatography-high resolution mass spectrometry (LC-HRMS). At the same concentration, EESB and WESB demonstrated effective antioxidant abilities when compared to standards. In addition, EESB demonstrated IC50 values of 1.946 µg/mL against acetylcholinesterase (AChE), 0.815 µg/mL against α-glycosidase and 0.675 µg/mL against α-amylase enzymes.

Synthesis and carbonic anhydrase isoenzymes I, II, IX, and XII inhibitory effects of dimethoxybromophenol derivatives incorporating cyclopropane moieties.

Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which after bromination with Br2 gave two isomeric monobromides (11 and 15), four isomeric dibromides (12, 13, 16, and 17), and two isomeric tribromides (14 and 18). The carboxylic acids 7, 8, and 19-26 were thereafter obtained by hydrolysis of the synthesized esters. All these bromophenol derivatives were tested against human (h) CA isoenzymes I and II (cytosolic, ubiquitous isoforms) and hCA IX and XII (transmembrane, tumor-associated enzymes). All tested bromophenols exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 0.54-59 nM against hCA I and in the range of 0.97-12.14 nM against hCA II, whereas they were low micromolar inhibitors against hCA IX and XII. The best hCA I inhibition was observed in new bromophenol derivative 20 (Ki = 0.54 nM). On the other hand, new bromophenol derivative 12 showed a powerful inhibition effect against hCA II (Ki = 0.97 nM).