Benzoylquinazolinone derivatives as new potential antidiabetic agents: α-Glucosidase inhibition,kinetic, and docking studies

Benzoylquinazolinone derivatives 3a–n were synthesized via a simple one-step reaction, and evaluated for in vitro α-glucosidase inhibitory activity. Compounds 3d , 3f–g , 3i , and 3m–n showed more inhibitory activity than standard drug acarbose (IC₅₀ = 750.0 ± 1.5 μM), and among them, compound 3d displayed the highest α-glucosidase inhibitory activity (IC₅₀ = 261.6 ± 0.1 μM). The kinetic analysis of the compound 3d revealed that this compound inhibited α-glucosidase in a competitive manner (K_i = 255 μM). The docking studies were applied to predict binding modes of the synthesized compounds in active site of α-glucosidase.     

Synthesis,Enzyme Inhibition,and Molecular Docking Studies of Hydrazones from Dichlorophenylacetic Acids

A series of hydrazones 5a–i were synthesized by the condensation of hydrazides derived from dichlorophenylacetic acids with different aromatic aldehydes and ketones. Their structures were confirmed by spectroscopic data and elemental analysis. Hydrazones 5a–i were evaluated for α‐glucosidase and urease inhibition activities. Five compounds exhibited potent α‐glucosidase inhibitory potential with IC₅₀ values 8.5 ± 0.3, 22.2 ± 0.78, 32.9 ± 1.5, 34 ± 2.4, and 170.6 ± 7.5 μM, respectively, which are many times better than that of the standard inhibitor acarbose (IC₅₀ = 840 ± 1.73 μM). Furthermore, molecular docking study was performed to explore the binding mode in the active sites of α‐glucosidase and urease enzymes.     

GC-MS analysis of metabolites from soxhlet extraction,ultrasound-assisted extraction and supercritical fluid extraction of Salacca zalacca flesh and its alpha-glucosidase inhibitory activity

Abstract

Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18?±?4.35%), whereas SFE_1 showed the lowest yield (0.42?±?0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC₅₀ values in comparison to that of quercetin, the positive control (IC₅₀ = 2.7?±?0.7?μg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC₅₀ = 724.3?±?42.9?μg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC₅₀ = 16.2?±?2.4?μg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.     

α-Glucosidase Inhibition and Antioxidant Properties of Streptomyces sp.: In Vitro

Streptomyces strain isolated from the soil sediment was studied for its in vitro α-glucosidase and antioxidant properties. Morphological characterization and 16S rRNA partial gene sequencing were carried out to confirm that the strain Loyola AR1 belongs to genus Streptomyces sp. Modified nutrient glucose broth was used as the basal medium for growth and metabolites production. Ethyl acetate extract of Loyola AR1 (EA-Loyola AR1) showed 50 % α-glucosidase inhibition at the concentration of 860.50?±?2.68 μg/ml. Antioxidant properties such as total phenolic content of EA-Loyola AR1 was 176.83?±?1.17 mg of catechol equivalents/g extracts. EA-Loyola AR1 showed significant scavenging activity on 2,2-diphenyl-picrylhydrazyl (50 % inhibition (IC₅₀), 750.50?±?1.61 μg/ml), hydroxyl (IC₅₀, 690.20?±?2.38 μg/ml), nitric oxide (IC₅₀, 850.50?±?1.77 μg/ml), and superoxide (IC₅₀, 880.08?±?1.80 μg/ml) radicals, as well as reducing power. EA-Loyola AR1 showed strong suppressive effect on lipid peroxidation (IC₅₀, 670.50?±?2.52 μg/ml). Antioxidants of β-carotene linoleate model system reveals significantly lower than butylated hydroxyanisole.     

Design,synthesis, biological evaluation,and docking study of new acridine-9-carboxamide linked to 1,2,3-triazole derivatives as antidiabetic agents targeting α-glucosidase

A new series of acridine-9-carboxamide-1,2,3-triazole derivatives 7a-m were designed, synthesized, and evaluated as novel α-glucosidase inhibitors. Acridine-9-carboxamide-1,2,3-triazole scaffold has been designed by combination of effective moieties from potent α-glucosidase inhibitors. Most of the synthesized compounds were more potent than standard inhibitor acarbose. Among the title compounds, the most potent compounds were compounds 7j , 7k , and 7a with IC₅₀ values of 120.2 ± 1.0, 151.1 ± 1.4, and 157.6 ± 1.6 μM, respectively (IC₅₀ value of acarbose = 750.0 ± 10.0 μM). Docking study of the most potent compounds demonstrated that these compounds formed stable complexes with α-glucosidase active site. Anti-α-amylase assay of compounds 7j , 7k , and 7a was performed and no activity was observed. in vitro cytotoxicity assay of the latter compounds revealed that these compounds were not cytotoxic toward human normal (HDF) and cancer (MCF-7) cell lines. ADME and toxicity prediction of compounds 7j , 7k , and 7a were also performed.     

Design,synthesis, in vitro and in silico studies of naproxen derivatives as dual lipoxygenase and α-glucosidase inhibitors

A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC₅₀ 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC₅₀ 36.53 ± 0.51 µM) and 4d (IC₅₀ 49.62 ± 0.12 µM) against standard drug baicalein (IC₅₀ 22.46 ± 1.32 µM) and quercetin (IC₅₀ 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC₅₀ 1.13 ± 0.62 µM ?123.47 ± 0.37 µM. Among these compounds, 4e (IC₅₀ 1.13 ± 0.62 µM), 5b (IC₅₀ 1.19 ± 0.43 µM), 8c (IC₅₀ 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC₅₀ 4.86 ± 0.14 µM), and baicalein (IC₅₀ 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC₅₀ 1.0 ± 1.13 µM ? 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC₅₀ 375.82 ± 1.76 µM), while compound 6c (IC₅₀ 1.0 ± 1.13 µM) and 7c (IC₅₀ 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.     

Identification of novel oxadiazole-based benzothiazole derivatives as potent inhibitors of α-glucosidase and urease: Synthesis,in vitro bio-evaluation and their in silico molecular docking study

This research work represents a synthetic approach for the development of hybrids derivatives of oxadiazole-based benzothiazole (1–17) and diversity in derivatives was achieved using variety of aryl ring of S-substituted benzothiazole to see the effect on the biological activities. All the synthesized derivatives were evaluated for their in vitro α-glucosidase and urease inhibitory potential. The α-glucosidase and urease inhibition profile of the new derivatives represents moderate to good inhibitory potential with IC₅₀ values ranging from 4.60 ± 1.20 µM to 48.40 ± 7.70 µM (α-glucosidase) and 8.90 ± 2.80 to 57.30 ± 7.70 µM (urease) respectively. The results were compared to standard acarbose (38.60 ± 4.50 µM) and thiourea (58.70 ± 6.80 µM) drugs respectively. Among the synthesized series, the analogs 1 having IC₅₀ values of and 4.60 ± 1.20 (α-glucosidase), 8.90 ± 2.80 (urease) and 2 with IC₅₀ values of 5.60 ± 1.60 (α-glucosidase) and 10.90 ± 2.10(urease) were found to be significantly active against targeted α-glucosidase and urease enzymes. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, ¹H- and ¹³C- NMR spectroscopy. The molecular docking studies of the synthesized derivatives showed good correlations with the experimental findings. The binding modes of active compounds and their interactions with active site residues revealed them as possible anti-diabetics and anti-urease leads. The degree of activity and docking studies displayed by the novel innovative structural hybrids of oxadiazole-based benzothiazole moieties make these compounds new active leads and promising candidates for the development of anti-diabetics and anti-urease agents.     

Peripheral or nonperipheral tetra‐[4‐(9H‐carbazol‐9‐yl)phenoxy] substituted cobalt(II), manganese(III) phthalocyanines: Synthesis,acetylcholinesterase, butyrylcholinesterase,and α‐glucosidase inhibitory effects and anticancer activities

In this work, peripheral or nonperipheral tetra‐[4‐(9H‐carbazol‐9‐yl)phenoxy] substituted cobalt(II), manganese (III) phthalocyanines were synthesized for the first time. Their acetylcholinesterase from Electrophorus electricus (AChE), butyrylcholinesterase equine serum (BuChE), and α‐glucosidase Saccharomyces cerevisiae inhibition were investigated spectrophotometrically. Finally, in vitro cytotoxicities of the compounds were investigated on human neuroblastoma (SH‐SY5Y) cell line using MTT cell viability assay. The compounds inhibited to enzymes in the range of 7.39 ± 0.25–35.29 ± 2.49 μM with IC₅₀ values for AChE and 14.38 ± 0.66–58.02 ± 4.94 μM for BuChE as compared with galantamine, which used as a positive control. For α‐glucosidase, all compounds had stronger inhibition action than acarbose according to the IC₅₀ values. The IC₅₀ values of N? Co and N? Mn were found to be 3.05 ± 0.10 and 15.82 ± 1.85 μM, respectively. The results of cytotoxicity showed that the IC₅₀ values were above 100 μM showing the compounds had low cytotoxic action against SH‐SY5Y cell line for 24 h. Overall, carbazole substituted nonperipheral compounds can be considered as a potential agent for the treatment of Alzheimer's diseases and diabetes mellitus.     

Synthesis of novel tetra-substituted benzimidazole compounds containing certain heterostructures with antioxidant and anti-urease activities

A new series of 5,6-dimethyl-2-phenyl-1H-benzimidazole derivatives was synthesized. The antioxidant activities of the synthesized compounds were determined according to the cupric reducing antioxidant capacity (CUPRAC), ABTS, and DPPH assays. Many of the target compounds showed good antioxidant activity. Among these compounds, it has been determined that the carbothioamide and 1,2,4-triazole derivatives had a very good antioxidant capacity. Also, all compounds were screened for in vitro inhibitory activity against Jack bean urease. Among the synthesized molecules, the starting compound, acetate, and acetohydrazide derivatives (with IC₅₀ values 12.02, 11.40, and 8.04 μg/mL, respectively) had a higher inhibitory effect on urease and exhibited a lower IC₅₀ values than acetohydroxamic acid (IC₅₀: 20.50 μg/mL) and thiourea (IC₅₀: 14.04 μg/mL) as a reference inhibitors.     

Synthesis characterization and evaluation of novel triazole based analogs as a acetylcholinesterase and α-glucosidase inhibitors

A series of novel triazole analogs (10a-k) bearing piperidine were synthesized in an aprotic solvent on the most effective pharmacophore with acetylcholinesterase (AChE) and α-glucosidase inhibitory activity. Triazole analogs (10a-k) were obtained in excellent yields (75–90 %) and characterized by EI-MS, IR, ¹³C NMR and ¹H NMR. The newly synthesized triazole analogs (10a-k) showed potent AChE inhibitory activity in the range of K_i = 0.0155 ± 1.25 µM to 0.557 ± 0.50 µM, IC₅₀ = 0.031 ± 0.85 to 0.537 ± 0.76 µM than Eserine (0.04 ± 0.001 µM) having strong electron-withdrawing fluorine group on the pyridine ring was recorded as a most potent inhibitor of AChE while (%) inhibition against α-glucosidase was ranging between 52.36 ± 1.67 to 85.35 ± 1.39. The kinetic study predicted that triazole analogs (10a-k) followed the un-competitive and mixed type of inhibition against AChE. In silico molecular docking was performed at the active site of the AChE co-crystal structure (PDB ID:1NEN). The results of molecular docking corelate will with the experimental findings.     

Potential enzyme inhibitor triazoles from aliphatic esters: Synthesis,enzyme inhibition and docking studies

Enzyme inhibitors are vital aspects for studying enzymes and are employed as drugs to treat certain disorders, thus implying pivotal role in drug discovery. In the current study, a series of triazole compounds 4(a-o) were synthesised to explore their inhibitory potential against α-glucosidase and urease enzymes. These derivatives with dichlorophenyl substituents were prepared by cyclization of thiosemicarbazides and their structures were confirmed through spectroanalytical techniques. The in vitro biological screening revealed that the compounds 4a, 4b, 4k, 4l, 4m, 4o having IC₅₀ values of 121.09 ± 1.25, 137.22 ± 0.22, 110.4 ± 2.4, 114.79 ± 1.1, 146.72 ± 1.29, 94.21 ± 0.15 [µM] respectively, exhibited good potential α-glucosidase inhibition, in comparison to Acarbose: IC₅₀ 51.23 µM, while the compounds 4a, 4b, 4c, 4k, 4l, having IC₅₀ values of 48.52 ± 0.39, 52.22 ± 1.37, 60.98 ± 0.34, 37.06 ± 0.51, 38.66 ± 1.7 [µM] respectively exhibited good potential for urease inhibition near to standard(Thiourea: IC₅₀ 24.14 [µM]). These in vitro findings were accompanied further by molecular docking simulations, which revealed significant binding interactions of the synthesized derivatives within the active sites of the enzymes.     

Betulinic acid derivatives: a new class of α-glucosidase inhibitors and LPS-stimulated nitric oxide production inhibition on mouse macrophage RAW 264.7 cells

Chemical manipulation studies were conducted on betulinic acid (1), twenty-one new rationally designed analogues of 1 with modifications at C-28 were synthesized for their evaluation of inhibitory effects on α-glucosidase and LPS-stimulated nitric oxide production in mouse macrophage RAW 264.7 cells. Compound 2 (IC₅₀ = 5.4 μM) exhibited an almost 1.4-fold increase in α-glucosidase inhibitory activity on yeast α-glucosidase while analogues 5 (IC₅₀ 16.4 μM) and 11 (IC₅₀ 16.6 μM) exhibited a 2-fold enhanced inhibitory activity on NO-production than betulinic acid.     

Synthesis and biological evaluation of some 1,3-benzoxazol-2(3H)-one hybrid molecules as potential antioxidant and urease inhibitors

A new series of 1,3-benzoxazol-2(3H)-one hybrid compounds, including coumarin, isatin 1,3,4-triazole and 1,3,4-thiadiazole moieties, were synthesized and biologically evaluated for their antioxidant capacities and anti-urease properties. The synthesized benzoxazole-coumarin ( 6a–e ) and benzoxazole-isatin ( 10a–c ) hybrids showed remarkable urease inhibitory activities with IC₅₀ (μM), ranging from 0.0306 ± 0.0030 to 0.0402 ± 0.0030, while IC₅₀ of standard thiourea is 0.5027 ± 0.0293. The synthesized benzoxazole-triazole ( 8a–c ) and benzoxazole-thiadiazole ( 9a–c ) hybrids showed similar urease inhibitory activities with IC₅₀ (μM), ranging from 0.3861 ± 0.0379 to 0.5126 ± 0.0345. The antioxidant activity of the synthesized compounds was evaluated for their antioxidant activities, such as reducing power and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging. The results of ABTS radical scavenging activities of some of the synthesized molecules showed higher activities than standard Trolox, SC₅₀ (μM) = 213.04 ± 18.12. One benzoxazole-coumarin ( 6f ), two benzoxazole-isothiocyanate ( 7b, 7c ), and two benzoxazole-triazole ( 8b, 8c ) derivatives showed higher activities (SC₅₀ (μM) values, 82.07 ± 10.34, 120.19 ± 7.30, 104.58 ± 10.55, 153.26 ± 7.14, and 144.82 ± 10.68, respectively) than standard Trolox, (SC₅₀ (μM) = 213.04 ± 18.12).     

Novel silver(I)N-heterocyclic carbene complexes bearing 2-(4-hydroxyphenyl)ethyl group: Synthesis,characterization, and enzyme inhibition properties

Herein, novel silver-based N-heterocyclic carbene (NHC) complexes bearing 2-(4-hydroxyphenyl)ethyl group were synthesized. Novel Ag(I)NHC complexes were synthesized from the 2-(4-hydroxyphenyl)ethyl-substituted benzimidazolium salts and silver oxide via in situ deprotonation method. The successful formation of all Ag(I)NHC complexes was proved by using ¹H NMR, ¹³C NMR, FTIR spectroscopy, and elemental analysis techniques. In addition, their inhibitory effects have been investigated of these substances on acetylcholinesterase (AChE), α-glycosidase (α-Gly), human carbonic anhydrase I (hCA I), and human carbonic anhydrase II (hCA II) enzymes. It has been seen that all compounds have a better ability to inhibit compared with existing tried inhibitors. Among these, the best inhibitor against AChE enzyme is 1g (K_i : 9.54 ± 0.98 μM and IC₅₀ : 17.40), and against α-Gly, 1c showed the highest effect (K_i 3.09 ± 0.36 μM and IC₅₀ 7.91). The best inhibitor against hCA I and hCA II enzymes are 1c and 1g compounds. For hCA I and hCA II, IC₅₀ values were calculated as 17.85 and 9.06 μM and K_i values were measured as 5.45 ± 2.02 and 8.99 ± 2.02 μM, respectively.     

Urease inhibitory profile of extracts and chemical constituents of Pistacia atlantica ssp. cabulica Stocks

The current study was designed to evaluate the urease inhibitory profile of extract and fractions of Pistacia atlantica ssp. cabulica Stocks followed by bioactivity-guided isolated compounds. The crude extract was found significantly active with urease inhibitor (95.40% at 0.2 mg/mL) with IC₅₀ values of 32.0 ± 0.28 μg/mL. Upon fractionation, ethyl acetate fraction displayed 100% urease inhibition with IC₅₀ values of 19.9 ± 0.51 μg/mL at 0.2 mg/mL. However, n-hexane and chloroform fractions exhibited insignificant urease inhibition. Similarly, the isolated compound, transilitin (1) and dihydro luteolin (2) demonstrated marked urease attenuation with 95 and 98% respectively, at 0.15 mg/mL. Both the isolated compounds showed marked potency with IC₅₀ values of 8.54 ± 0.54 and 9.58 ± 2.22 μg/mL, respectively. In short, both the extract and fractions and isolated compounds showed marked urease inhibition and thus a useful natural source of urease inhibition.     

Synthesis and anti-α-glucosidase activity evaluation of betulinic acid derivatives

In this article, a series of betulinic acid derivatives (3a ～ 3u, 4a ～ 4e) were synthesized through a stepwise structure optimization and evaluated for their anti-α-glucosidase activities. All synthesized derivatives exhibited stronger anti-α-glucosidase activities (IC₅₀: 0.56 ± 0.05 ～ 3.99 ± 0.23 μM) than betulinic acid (IC₅₀: 7.21 ± 0.58 μM) and acarbose (IC₅₀: 611.45 ± 15.51 μM). Compound 3q presented the outstanding inhibitory activity (IC₅₀: 0.56 ± 0.05 μM), which was ～ 1100 time stronger than that of acarbose. Compound 3q was revealed as a reversible and noncompetitive α-glucosidase inhibitor by inhibitory mechanism assay. Fluorescence spectra, 3D fluorescence and CD spectra results showed that the interaction of compound 3q with α-glucosidase caused the conformational and secondary structure content change of α-glucosidase. Finally, the molecular docking simulated the interaction between compound 3q with α-glucosidase and the physicochemical parameter was assessed using SwissADME software.     

Synthesis, α-glucosidase inhibition and molecular docking studies of natural product 2-(2-phenyethyl)chromone analogues

A series of natural product (2-phenyethyl)chromone analogues (3–34) were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results indicated that some of the synthesized derivatives displayed inhibitory activities against α-glucosidase with IC₅₀ values ranging from 11.72 ± 0.08 to 85.58 ± 2.30 μM when compared to the standard drug acarbose (IC₅₀ = 832.22 ± 2.00 μM). Among them, compound 4 with a hydroxyl group at the 7-position of chromone and a chloro group at the 4-position of the benzene ring, displayed the most significant inhibitory activity with the IC₅₀ value of 11.72 ± 0.08 μM. The inhibitory mechanism of compound 4 against α-glucosidase was studied by enzyme kinetic, circular dichroism spectra, fluorescence quenching, and molecular docking. Sucrose loading test in vivo further demonstrated that it could decrease blood glucose levels after sucrose administration in normal Kunming mice. In vitro cytotoxicity showed that 4 exhibited low cytotoxicity against normal human cell lines. The ADME study suggested that all compounds are likely to be orally active as they obeyed Lipinski’s rule of five. In summary, our studies showed that these derivatives are a new class of α-glucosidase inhibitors.     

New metal complexes of sulfonamide: Synthesis,characterization, in‐vitro anticancer,anticholinesterase, antioxidant,and antibacterial studies

In this research work a sulfonamide from tranexamic acid has been synthesized followed by its metal complexation. p‐Bromo benzene sulfonyl chloride was used to synthesize sulfonamide using eco‐friendly atmosphere. The sulfonamide prepared from tranexamic acid has been utilized for the preparation of metal complexes with various metals like Ni, Cu, Co, Mn, Pb, Cd, Cr, Fe, Sn, and Sr. All synthesized compounds were characterized by applying different spectral techniques such as Fourier‐transform infrared (FTIR), mass spectrometry, and X‐ray diffraction (XRD) analysis. The biological activities such as radical scavenging activity, enzyme inhibition, antifungal, antibacterial, and anticancer were performed. It was concluded from the results that compounds showed moderate to good activity. Cu complex of sulfonamide showed the highest antioxidant potential (87.69 ± 1.8% with IC₅₀ 137 ± 1.0 μg) while Cr complex depicted the highest activity against both enzymes; AChE (73.51 ± 1.7% with IC₅₀ 165 ± 1.1 μg) and BChE (70.05 ± 1.3% with IC₅₀ 152 ± 1.8 μg). Mn complex showed good results against six bacterial strains comparable with standard drug. Cr complex depicted highest anticancer activity against MCF7 and human corneal epithelial cell (HCEC) cell lines 45.73% and 25.40%, respectively. These results concluded that metal complexes of sulfonamide may be good induction in the future for medical purposes.     

Phenolic composition,antioxidant and enzyme inhibitory activities of Parkia biglobosa (Jacq.) Benth., Tithonia diversifolia (Hemsl) A. Gray,and Crossopteryx febrifuga (Afzel.) Benth

Medicinal plants from Chad grow under special climatic conditions in between the equatorial forest of Central Africa and the desert of North Africa and are understudied. Three medicinal plants from Chad (T. diversifolia, P. Biglobosa and C. Febrifuga) were evaluated for their phenolic composition, antioxidant and enzyme inhibition activities. The total phenolic composition varied from 203.19 ± 0.58 mg GAE/g DW in the ethyl acetate extract of P. biglobosa, to 56.41 ± 0.89 mg GAE/g DW in the methanol extract of C. febrifuga while the total flavonoid content varied from 51.85 ± 0.91 mg QE/g DW in the methanol extract of P. biglobosa to 08.56 ± 0.25 mg QE/g DW in the methanol extract of C. febrifuga. HPLC-DAD revealed that rutin, gallic acid and protocatechuic acid were the most abundant phenolics in T. diversifolia, P. Biglobosa and C. Febrifuga respectively. The antioxidant activity assayed by five different methods revealed very good activity especially in the DPPH^?, ABTS^?+ and CUPRAC assays where the extracts were more active than the standard compounds used. Good inhibition was exhibited against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with methanol (IC₅₀: 15.63 ± 0.72 µg/mL), ethyl acetate (IC₅₀: 16.20 ± 0.67 µg/mL) extracts of P. biglobosa, and methanol (IC₅₀: 21.53 ± 0.65 µg/mL) and ethyl acetate (IC₅₀: 30.81 ± 0.48 µg/mL) extracts of T. diversifolia showing higher inhibition than galantamine (IC₅₀: 42.20 ± 0.44 µg/mL) against BChE. Equally, good inhibition was shown on α-amylase and α-glucosidase. On the α-glucosidase, the ethyl acetate (IC₅₀ = 12.47 ± 0.61 µg/mL) and methanol extracts (IC₅₀ = 16.51 ± 0.18 µg/mL) of P. biglobosa showed higher activity compared to the standard acarbose (IC₅₀ = 17.35 ± 0.71 µg/mL) and on α-amylase, the ethyl acetate (IC₅₀ = 13.50 ± 0.90 µg/mL) and methanol (IC₅₀ = 18.12 ± 0.33 µg/mL) extracts of P. biglobosa showed higher activity compared to acarbose (IC₅₀ = 23.84 ± 0.25 µg/mL). The results indicate that these plants are good sources of antioxidant phenolics and can be used to manage oxidative stress linked illnesses such as Alzheimer’s disease and diabetes.     

Structure activity relationship of bergenin,p-hydroxybenzoyl bergenin, 11-O-galloylbergenin as potent antioxidant and urease inhibitor isolated from Bergenia ligulata

Ethanol extract of the aerial parts of Bergenia ligulata was subjected to solvent–solvent separation followed by various chromatographic techniques that lead to isolation of bergenine (1), p-hydroxybenzoyl bergenin (2), 11-O-galloylbergenin (3) and methyl gallate (4) as major constituents. Ethyl acetate fraction showed a dose-dependent urease inhibitory pattern with IC₅₀ value of 54μg/mL. Structures of compounds 1 and 3 were established by XRD and 2, 4 by NMR. All these compounds were subjected to DPPH scavenging activity, reducing power assay and urease inhibitory activity. The EC₅₀ 7.45 ± 0.2 μg/mL and 5.39 ± 0.28 μg/mL values in terms of antioxidant and reducing power, respectively, were less for 3. Compounds 1–3 showed moderate to significant urease inhibitory potential with IC₅₀ 57.1 ± 0.7, IC₅₀ 48.4 ± 0.3 and 38.6 ± 1.5. Antioxidant activities and urease inhibitory potential were investigated and compound 3 was found to be the most active.