Exploring the therapeutic potential of Derris elliptica (Wall.) Benth in Streptozotocin-Induced diabetic Rats: Phytochemical characterization and antidiabetic evaluation.

Derris elliptica (Wall.) Benth, a native medicinal plant, has been used to treat diabetes for centuries; however, comprehensive documentation of its bioactive constituents and therapeutic effectiveness is lacking. In this study, we investigated the phytochemical profile and antidiabetic potential of D. elliptica methanolic leaf extract (DEME) in diabetic Sprague Dawley rats induced with streptozotocin (STZ). In normal rats, acute oral toxicity evaluations were conducted, and in STZ-induced rats, antidiabetic properties were investigated. 14 days of oral administration of standard glibenclamide and the extract at 200 and 400 mg/kg body weight to diabetic rodents. Assessed parameters included blood glucose levels, alterations in body weight, biochemical markers, and histological analysis of the pancreas, liver, and kidney. Numerous phytoconstituents were uncovered through qualitative phytochemical assays, 1H NMR, and 1H-13C HSQC screening. Quercetin was identified by 1H NMR characterization, and a ceramide analogue compound was isolated and partially characterized by 1H NMR. There were no indications of toxicity or mortality. The treatment with DEME significantly (p < 0.001) decreased body weight and had a remarkable hypoglycemic effect. Both 200 mg/kg and 400 mg/kg extract concentrations decreased total cholesterol levels significantly (p < 0.01 and p < 0.05, respectively). In addition, glibenclamide and the 400 mg/kg dose of extract increased serum insulin levels substantially (p < 0.05) and decreased total bilirubin, lactic acid dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels. In addition to glibenclamide, treatment with DEME has exhibited cytoprotective effects and increased insulin secretion, thereby exerting a potent antihyperglycemic effect. These results suggest that D. elliptica may have therapeutic potential for the treatment of diabetes mellitus.

Synthesis, Characterization, and Biological Evaluation of 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl Butanoic Acid Derivatives.

This study aimed to evaluate 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, 1HNMR, and 13CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme's active site.

Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors.

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1-21) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.

Multitargeted Molecular Docking and Dynamic Simulation Studies of Bioactive Compounds from Rosmarinus officinalis against Alzheimer's Disease.

Alzheimer's disease (AD) has been associated with the hallmark features of cholinergic dysfunction, amyloid beta (Aß) aggregation and impaired synaptic transmission, which makes the associated proteins, such as ß-site amyloid precursor protein cleaving enzyme 1 (BACE I), acetylcholine esterase (AChE) and synapsin I, II and III, major targets for therapeutic intervention. The present study investigated the therapeutic potential of three major phytochemicals of Rosmarinus officinalis, ursolic acid (UA), rosmarinic acid (RA) and carnosic acid (CA), based on their binding affinity with AD-associated proteins. Detailed docking studies were conducted using AutoDock vina followed by molecular dynamic (MD) simulations using Amber 20. The docking analysis of the selected molecules showed the binding energies of their interaction with the target proteins, while MD simulations comprising root mean square deviation (RMSD), root mean square fluctuation (RMSF) and molecular mechanics/generalized born surface area (MM/GBSA) binding free energy calculations were carried out to check the stability of bound complexes. The drug likeness and the pharmacokinetic properties of the selected molecules were also checked through the Lipinski filter and ADMETSAR analysis. All these bioactive compounds demonstrated strong binding affinity with AChE, BACE1 and synapsin I, II and III. The results showed UA and RA to be potential inhibitors of AChE and BACE1, exhibiting binding energies comparable to those of donepezil, used as a positive control. The drug likeness and pharmacokinetic properties of these compounds also demonstrated drug-like characteristics, indicating the need for further in vitro and in vivo investigations to ascertain their therapeutic potential for AD.

Antibacterial Effects of Flavonoids and Their Structure-Activity Relationship Study: A Comparative Interpretation.

According to the latest report released by the World Health Organization, bacterial resistance to well-known and widely available antibacterial drugs has become a significant and severe global health concern and a grim challenge to tackle in order to cure infections associated with multidrug-resistant pathogenic microorganisms efficiently. Consequently, various strategies have been orchestrated to cure the severe complications related to multidrug-resistant bacteria effectively. Some approaches involved the retardation of biofilm formation and multidrug-resistance pumps in bacteria as well as the discovery of new antimicrobial agents demonstrating different mechanisms of action. In this regard, natural products namely alkaloids, terpenoids, steroids, anthraquinone, flavonoids, saponins, tannins, etc., have been suggested to tackle the multidrug-resistant bacterial strains owing to their versatile pharmacological effects. Amongst these, flavonoids, also known as polyphenolic compounds, have been widely evaluated for their antibacterial property due to their tendency to retard the growth of a wide range of pathogenic microorganisms, including multidrug-resistant bacteria. The hydroxylation of C5, C7, C3', and C4'; and geranylation or prenylation at C6 have been extensively studied to increase bacterial inhibition of flavonoids. On the other hand, methoxylation at C3' and C5 has been reported to decrease flavonoids' antibacterial action. Hence, the latest information on the antibacterial activity of flavonoids is summarized in this review, with particular attention to the structure-activity relationship of this broad class of natural compounds to discover safe and potent antibacterial agents as natural products.

Synthesis of New Triazole-Based Thiosemicarbazone Derivatives as Anti-Alzheimer's Disease Candidates: Evidence-Based In Vitro Study.

Triazole-based thiosemicarbazone derivatives (6a-u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

N-Sulfonated derivatives of (2-furoyl)piperazine: Promising antibacterial agents with mild cytotoxicity.

2-Furoyl-1-piperazine (1) was treated with a series of alkyl/aryl sulfonyl chlorides (2a-i) under benignant conditions to obtain its N-sulfonated derivatives (3a-i). These compounds were screened for their antibacterial potential against pathogenic bacteria. The low Minimum Inhibitory Concentration (MIC) values of these molecules, in comparison of ciprofloxacin, demonstrated their high antibacterial potential. Cytotoxic activities were ascertained through their hemolytic potential and mild hemolytic profiles of these compounds proved them to be promising compounds for drug designing and development.

Synthesis of novel N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{[5-(un/substituted-phenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as potent antibacterial agents.

The synthetic methodology was initiated by reacting 1,4-benzodioxane-6-amine (1) with 2-bromoacetyl bromide (2) in aqueous alkaline media under dynamic pH control to get compound 2,3-dihydro-1,4-benzodioxin-6-yl-2-bromoacetamide (3). In the subsequent reactions, a variety of un/substituted-benzoic acids (4a-k), through a succession of three steps, was converted into respective oxadiazole nucleophiles, 7a-k. Finally, the targeted molecules, 8a-k, were obtained by reacting 7a-k with electrophile 3 in an aprotic polar solvent. These compounds were corroborated by spectral characterization like IR, EI-MS, 1H-NMR, and CHN analysis data. These molecules were screened for their antibacterial potential and most of them exhibited a potent activity. Moreover, their cytotoxicity was profiled through hemolytic activity and it was observed that majority of them was very modest in toxicity.

Synthesis and evaluation of novel 1, 2, 4-substituted triazoles for urease and anti-proliferative activity.

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenyl-hydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propan-amides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and anti-proliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methyl-phenyl)propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Anti-proliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study.

REPORT - Synthesis of promising antibacterial and antifungal agents: 2-[[(4-Chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(un/substituted-phenyl)acetamides.

In the presented work, 2,3-dihydro-1,4-benzodioxin-6-amine (1) was reacted with 4-chlorobenzenesulfonyl chloride (2) in presence of aqueous basic aqueous medium to obtain 4-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzenesulfonamide (3). In parallel, various un/substituted anilines (4a-l) were treated with bromoacetyl bromide (5) in basified aqueous medium to obtain corresponding 2-bromo-N-(un/substituted)phenylacetamides (6a-l) as electrophiles. Then the compound 3 was finally reacted with these electrophiles, 6a-l, in dimethylformamide (DMF) as solvent and lithium hydride as base and activator to synthesize a variety of 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(un/substituted)phenylacetamides (7a-l). The synthesized compounds were corroborated by IR, 1H-NMR and EI-MS spectral data for structural confirmations. These molecules were then evaluated for their antimicrobial and antifungal activities along with their %age hemolytic activity. Some compounds were found to have suitable antibacterial and antifungal potential, especially the compound 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(3,5-dimethylphenyl)acetamide (7l) exhibited good antimicrobial potential with low value of % hemolytic activity.

Synthesis of some N-sulfonated derivatives of 1-[(E)-3-phenyl-2-propenyl]piperazine as suitable antibacterial agents.

In the planned research work, the nucleophilic substitution reaction of 1-[(E)-3-phenyl-2-propenyl]piperazine (1) was carried out with different sulfonyl chlorides (2a-g) at pH 9-10 to synthesize its different N-sulfonated derivatives (3a-g). The structures of the synthesized compounds were characterized by their proton-nuclear magnetic resonance (1H-NMR), carbon-nuclear magnetic resonance (13C-NMR) and Infra Red (IR) spectral data, along with CHN analysis. The inhibition potential of the synthesized molecules was ascertained against two bacterial pathogenic strains i.e. Bacillus subtilis and Escherichia coli. It was inferred from the results that some of the compounds were very suitable inhibitors of these bacterial strains. Moreover, their cytotoxicity was also profiled and it was outcome that most of these molecules possessed moderate cytotoxicity.

Report - Synthesis of new antibacterial agents encompassing tosyl, piperidine, propanamide and 1,3,4-oxadiazole functionalities.

A series of propanamide compounds 6a-l was derived by N-substitution reactions, encompassing tosyl, piperidine and 1,3,4-oxadiazole moieties. The intended array of compounds 6a-l was afforded by a series of five steps reaction scheme. 1-Tosylpiperidin-4-carboxylate (1) was synthesized by the reaction of tosyl chloride (a) with ethyl isonipecotate (b) under mild basic conditions. Compound 1 was subjected to nucleophillic substitution by hydrazine to synthesize 1-tosylpiperidin-4-carbohydrazide (2). The compound, 5-(1-tosylpiperidin-4-yl)-1,3,4-oxadiazole-2-thiol (3) was synthesized by intermolecular cyclization of compound 2 by CS2 under strong basic conditions. The target compounds, 6a-l, were finally synthesized from 3 by reacting with different electrophiles, 5a-l, in an aprotic polar solvent with sodium hydride as an activator. The different propanamoyl electrophiles, 5a-l, were synthesized by the reaction of different aromatic and aliphatic amines, 4a-l, with 3-bromopropionyl chloride under mild basic conditions. The structural elucidation was carried out using modern spectroscopic techniques including IR, 1H-NMR and EI-MS. The antibacterial potential of synthesized compounds was assessed against five bacterial strains. Compounds 6a, 6c, 6d, 6e and 6f were found to be potent antibacterial agents.

Synthesis, characterization, antibacterial, hemolytic and thrombolytic activity evaluation of 5-(3-chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives.

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.

Evaluation of the Enzyme Inhibitory and Antioxidant Activities of Entada spiralis Stem Bark and Isolation of the Active Constituents.

Digestive enzymes and free radical inhibitors are used to prevent complications resulting from diabetes. Entada spiralis (family Leguminosae), which is a well-known medicinal plant in herbal medicine due to its various traditional and medicinal applications, was studied. Crude extracts were successively obtained from the stem bark using petroleum ether, chloroform and methanol as extracting solvents. The antioxidant activity of all the extracts, fractions and isolated compounds were estimated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene and 2,2'-azinobis(-3-ethylbenzothiazine-6-sulfonic acid) (ABTS) assays, while digestive enzymes inhibitory activity was assessed using α-amylase and α-glucosidase inhibitory methods. Structure elucidation of pure compounds was achieved through different spectroscopic analysis methods. Fractionation and purification of the most active methanol extract resulted in the isolation of a ferulic ester namely; (e)-hexyl 3-(4-hydroxy-3-methoxyphenyl) acrylate (FEQ-2) together with five known phenolic constituents, identified as kaempferol (FEQ-3), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (FEQ-2), gallic acid (FEQ-5), (+)-catechin (FEQ-7) and (-)-epicatechin (FEQ-8). FEQ-5 exhibited the strongest antioxidant and enzyme inhibitory activities followed by FEQ-3 and FEQ-4. FEQ-2 also displayed potent free radical scavenging activity with IC50 values of 13.79 ± 2.13 (DPPH) and 4.69 ± 1.25 (ABTS) µg/mL, respectively. All other compounds were found active either against free radicals or digestive enzymes.

Synthesis of some new N-(alkyl/aralkyl)-N-(4-methoxyphenethyl) benzene sulfonamides as antibacterial agents against Escherichia.

The present study comprises the synthesis of a new series of benzenesulfonamides derived from N-sulfonation of 2-(4-methoxyphenyl)-1-ethanamine (1). The synthesis was initiated by the reaction of 2-(4-methoxyphenyl)-1-ethanamine (1) with benzenesulfonyl chloride (2), to yield N-(4-methoxyphenethyl)benzenesulfonamide (3). This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides (4a-j) in N,N-dimethylformamide (DMF) and in the presence of a weak base lithium hydride (LiH) to obtain various N-(alkyl/aralkyl)-N-(4-methoxyphenethyl) benzenesulfonamides (5a-j). The characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. Elemental analysis also supported this data. The biofilm inhibitory action of all the synthesized compounds was carried out on Escherichia coli and some of the compounds were identified to be very suitable inhibitors of this bacterial strain. Furthermore, the molecules were also tested for their cytotoxicity behavior to assess their utility as less cytotoxic therapeutic agents.

Synthesis of new S-substituted derivatives of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide as suitable antibacterial and anticancer agents with moderate cytotoxicity.

In the study presented here, the nucleophilic substitution reaction of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide was carried out with different alkyl/aralkyl halides (5a-r) to form its different S-substituted derivatives (6a-r), as depicted in scheme 1. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR and CHN analysis data. Bacterial biofilm inhibitory activity of all the synthesized compounds was carried out against Bacillus subtilis and Escherichia coli. The anticancer activity of these molecules was ascertained using anti-proliferation (SRB) assay on HCT 116 Colon Cancer Cell lines while the cytotoxicity of these molecules was profiled for their haemolytic potential. From this investigation it was rational that most of the compounds exhibited suitable antibacterial and anticancer potential along with a temperate cytotoxicity.

α-Glucosidase inhibitory potential and hemolytic evaluation of newly synthesized 3,4,5-trisubstituted-1,2,4-triazole derivatives.

A series of 1, 2, 4-triazole derivatives bearing piperidine moiety has been introduced as new anti-diabetic drug candidates with least cytotoxicity. p-Chlorophenylsulfonyl chloride (1) and ethyl nipecotate (2) were the starting reagents that resulted into corresponding 3,4,5-trisubstituted-1,2,4-triazole (6) through a series of steps. A series of electrophiles, 9a-e, were synthesized by reacting 4-bromobutyryl chloride (7) with differently substituted aromatic amines (8a-e) under basic aqueous medium. Target derivatives, 10a-e, were synthesized by the reaction of compound 6 with N-aryl-4-bromobutanamides (9a-e) in an aprotic solvent. Structures of all the derivatives were verified by spectroscopic analysis using IR, 1H-NMR, 13C-NMR and EIMS. Most of the derivatives revealed moderate to good α-glucosidase inhibitory activity with reference to acarbose. The moderate hemolytic potential demonstrated least toxicity.

Neuroprotective effects of Foeniculum vulgare seeds extract on lead-induced neurotoxicity in mice brain.

The present study investigates the neuroprotective effects of Foeniculum vulgare seeds in a lead (Pb)-induced brain neurotoxicity mice model. The dried seeds extract of Foeniculum vulgare was prepared with different concentrations of organic solvents (ethanol, methanol, n-hexane). The in vitro antioxidant activity of Foeniculum vulgare seed extracts was assessed through DPPH assay and the chemical composition of the extracts was determined by high-resolution 1H NMR spectroscopy. The age-matched male Balb/c mice (divided into 9 groups) were administered with 0.1% Pb and 75% and 100% ethanol extracts of Foeniculum vulgare seeds at a dose of 200 mg/kg/day and 20 mg/kg/day. The maximum antioxidant activity was found for 75% ethanol extract, followed by 100% ethanol extract. Gene expression levels of oxidative stress markers (SOD1 and Prdx6) and the three isoforms of APP (APP common, 770 and 695), in the cortex and hippocampus of the treated and the control groups were measured. Significant increase in APP 770 expression level while a substantial decrease was observed for SOD1, Prdx6 and APP 695 expression in Pb-treated groups. Interestingly, the deranged expression levels were significantly normalized by the treatment with ethanol extracts of Foeniculum vulgare seeds (specifically at dose of 200 mg/kg/day). Furthermore, the Pb-induced morphological deterioration of cortical neurons was significantly improved by the ethanol extracts of Foeniculum vulgare seeds. In conclusion, the present findings highlight the promising therapeutic potential of Foeniculum vulgare to minimize neuronal toxicity by normalizing the expression levels of APP isoforms and oxidative stress markers.

Synthesis of modified Schiff base appended 1,2,4-triazole hybrids scaffolds: elucidating the in vitro and in silico α-amylase and α-glucosidase inhibitors potential.

The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their α-amylase and α-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as 1H-NMR, 13C-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro α-glucosidase and α-amylase inhibitory activities of the synthesized compounds were evaluated in order to determine their potential anti-diabetic properties. All analogues showed varied range of inhibitory activity having IC50 values ranging from 17.09 ± 0.72 to 45.34 ± 0.03 µM (α-amylase) and 16.35 ± 0.42 to 42.31 ± 0.09 µM (α-glucosidase), respectively. Specifically, the compounds 1, 7 and 8 were found to be significantly active with IC50 values of 17.09 ± 0.72, 19.73 ± 0.42, and 23.01 ± 0.04 µM (against α-amylase) and 16.35 ± 0.42, 18.55 ± 0.26, and 20.07 ± 0.02 µM (against α-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC50 values of 13.02 ± 0.11 µM (for α-glucosidase) and 15.04 ± 0.02 µM (for α-amylase), respectively. The structure-activity relationship (SAR) studies were conducted based on differences in substituent patterns at varying position of aryl rings A and B may cause to alter the inhibitory activities of both α-amylase and α-glucosidase enzymes. Additionally, the molecular docking study was carried out to explore the binding interactions possessed by most active analogues with the active sites of targeted α-amylase and α-glucosidase enzymes.

Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights.

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

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