Effects Of Enzyme Inhibitors Research Articles

Comparative Analysis of Five Moroccan Thyme Species: Insights into Chemical Composition, Antioxidant Potential, Anti-Enzymatic Properties, and Insecticidal Effects

This study aimed to investigate the chemical composition and bioactivities of essential oils (EOs) from five Moroccan thyme species: Thymus broussonetii subsp. broussonetii, T. maroccanus, T. willdenowii, T. zygis subsp. gracilis, and T. satureioides, collected from various geographical regions. Gas chromatography–mass spectrometry (GC-MS) identified thymol, p-cymene, borneol, γ-terpinene, carvacrol, α-pinene, and camphene as major constituents, with variations across species. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) revealed important levels of calcium (450.6–712.2 mg/kg), potassium (255.4–420.7 mg/kg), magnesium (97.3–150.7 mg/kg), and iron (1.95–15.1 mg/kg). The EOs demonstrated strong antioxidant activity in DPPH, FRAP, and β-carotene bleaching assays. Insecticidal activity against Aphis gossypii revealed the highest efficacy with T. willdenowii EO (LC50 = 6.2 µL/mL), followed by T. maroccanus and T. zygis subsp. gracilis. Additionally, the EOs exhibited potent enzyme inhibitory effects at 1 mg/mL on acetylcholinesterase (83.1–96.4%), tyrosinase (77.5–89.6%), and α-glucosidase (79.4–89.5%). These findings suggest that thyme EOs, particularly from T. willdenowii, T. zygis, and T. maroccanus, are promising candidates for integrated pest management and natural enzyme inhibitors. Their potential applications in medicinal and pharmaceutical fields underscore the need for further research to optimize their use under specific conditions and dosages.

Research Progress of Food-Derived Antihypertensive Peptides in Regulating the Key Factors of the Renin-Angiotensin System.

Food protein-derived antihypertensive peptides have attracted substantial attention as a safer alternative for drugs. The regulation of the renin-angiotensin system (RAS) is an essential aspect underlying the mechanisms of antihypertensive peptides. Most of the identified antihypertensive peptides exhibit the angiotensin-converting enzyme (ACE) inhibitory effect. In addition, artificial intelligence has improved the efficiency of ACE inhibitory peptide identifications. Moreover, the inhibition of renin and blockade or down-regulation of angiotensin type I receptor (AT1R) have also been demonstrated to be effective intervention strategies. With the identification of the ACE2/Ang (1-7)/MasR axis, activation or up-regulation of angiotensin-converting enzyme 2 (ACE2) has also emerged as a new intervention pathway. This review summarizes the research progress of antihypertensive peptides in intervening with hypertension from the perspective of their properties, sources, and key factors. The objective of this review is to provide theoretical references for the development of antihypertensive peptides and the explorations of the molecular mechanisms.

Antihypertensive and Angiotensin I-Converting Enzyme-Inhibitory Effects of the Leaves of Sesamum indicum and Bioactive Compounds.

Sesame (Sesamum indicum L.) is an important oilseed crop, and its seeds are a source of edible oil and widely used as a nutritious food that is beneficial to health in oriental countries. Phytochemical and biological investigations of the seeds have been well reported; however, those of the leaves have been limited. To explore the potential value of sesame leaves, we focused on their antihypertensive potency. Oral administration of sesame leaf extract significantly reduced blood pressure in spontaneously hypertensive rats. Next, we examined the angiotensin I-converting enzyme (ACE)-inhibitory activity of sesame leaves, stems, and seeds and observed that the inhibitory potencies of leaves and seeds were stronger than those of stems. Acteoside and pedaliin, the major compounds in the leaves, as well as exhibited ACE inhibitory activity. Furthermore, we determined the content of these compounds in the leaves, stems, and seeds using LC/MS. The contents of both compounds in the leaves were higher than those in the stems and seeds. These results suggest that sesame leaf extract can mitigate hypertension, at least in part, via the inhibition of ACE activity by acteoside and pedaliin, suggesting that sesame leaves may have the potential to be used for treating hypertension.

Integration of InVitro and In Silico Results From Chemical and Biological Assays of Rheum turkestanicum and Calendula officinalis Flower Extracts.

In this study, we conducted a thorough analysis of Rheum turkestanicum (RT) and Calendula officinalis flowers (COF) extracts with varying polarities using LC-MS chemical profiling and biological tests (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic effects). The highest level of total phenolic content in the ethanol extract of RT with 75.82 mg GAE/g, followed by the infusions of RT (65.00 mg GAE/g) and COF (40.99 mg GAE/g). A total of 20 bioactive compounds were identified and quantified. The ethanol extract of COF was rich in terms of 5-O-caffeoylquinic acid (2780.56 μg/g), isorhamnetin-O-rutinoside (1653.59 μg/g), and rutin (1356.97 μg/g). However, RF extracts were rich in catechin gallate (21.66-80.01 μg/g) and 5-O-caffeoylquinic acid. Except for metal chelating ability, the ethanol extract of RT exhibited the strongest ability (DPPH: 171.5 mg TE/g; ABTS: 387.35 mg TE/g; CUPRAC: 449.80 mg TE/g; FRAP: 195.60 mg TE/g; and PBD: 1.52 mmol TE/g). In the enzyme inhibition tests, the tested ethanol extracts for both species were more active than the infusion. The highest values for tyrosinase were recorded as 72.47 mg KAE/g (in RT extracts) and 71.74 mg KAE/g (in COF extracts). Furthermore, all extracts underwent assessment for their antibacterial and antifungal properties, targeting both Gram-positive and Gram-negative bacteria, as well as clinical yeast and fungal microorganisms. In silico studies yielded valuable insights into the potential therapeutic applications of the bioactive compounds identified in COF and RT extracts. Stable interactions were observed between key compounds, such as isorhamnetin 3-O-glucoside and 3-O-caffeoylquinic acid, with crucial target proteins (AChE, BChE, and MurE). These compounds formed stable hydrogen bonds with minimal root mean square deviation (RMSD) fluctuations, particularly in the isorhamnetin 3-O-glucoside-Staphylococcus aureus MurE and 3-O-caffeoylquinic acid-MurE of S. aureus complexes. These findings further underscore the potential of these compounds as promising candidates for therapeutic development.

The Effects of Lamium garganicum L. Subsp. lasioclades (Stapf.) R. Mill Plant Against Fibroblast (U2OS Cell), Acetylcholinesterase, Glutathione S-Transferase: An In Vitro, In Silico Biological Activity Screening Study.

In this study, some biological activities of extracts of Lamium garganicum subsp. lasioclades (Lgl) have been evaluated as well as identified the phenolic composition. Concentration ranges of 31.25, 62.5, 125, 250, and 500µg/mL were applied to determine the extract's anticancer properties. Significant results were obtained against the osteosarcoma cell line (U2OS cell) compared to normal human umbilical vein endothelial cells (HUVEC). To determine the antioxidant activities, ABTS, DPPH, FRAP, and CUPRAC methods were studied in vitro. Enzyme inhibition effects of methanol extract against the glutathione S-transferase (GST) and acetylcholinesterase (AChE) enzymes were investigated. IC50 values were calculated as 12.96µL/mL for AChE and 13.02µg/mL for GST, respectively. The phenolic contents of the plant extract were analyzed by HPLC. The interaction mechanisms of protein-ligand complexes formed by AChE and GST receptors with gallic acid and rutin were investigated by molecular docking studies. The stability of the complexes formed between receptors and ligands was confirmed by root mean square deviation (RMSD), root mean square fluctuation (RMSF), number of average hydrogen bonding interactions (Hb), and radius of gyration (Rg) analyses obtained from 100ns molecular dynamics simulations.

Green synthesis, characterization, and in vitro and in vivo biological screening of iron oxide nanoparticles (Fe3O4) generated with hydroalcoholic extract of aerial parts of Euphorbia milii

Abstract In this work, iron oxide nanoparticles (IONPs) were synthesized using green methods. The structural morphological and optical properties of nanoparticles (NPs) were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), ultraviolet–visible spectroscopy, and Fourier transform infrared spectroscopy. Based on the SEM analysis, spherical NPs with a size distribution in the range of 50–70 nm were simulated with slight variations in shapes, and the corresponding XRD was calculated. The calculated XRD patterns were then averaged. Well-defined crystalline structure of a single-phase spinel structure and a spherical shape of IONPs were observed. The in vitro and in vivo biological activities of IONPs synthesized with the hydroalcoholic extract of Euphorbia milii’s aerial parts were studied. The antibacterial effects were evaluated against Staphylococcus aureus, and the enzyme inhibitory effects of the IONPs and E. milii extract on various enzymes were assessed. The IONPs demonstrated significant inhibitory activity against urease (89.09% inhibition), α-glucosidase (72.87% inhibition), carbonic anhydrase II (87.09% inhibition), and xanthine oxidase (85.09% inhibition). The E. milii extract also exhibited considerable inhibition of these enzymes. The IC50 values for urease, α-glucosidase, carbonic anhydrase II, and xanthine oxidase inhibition by IONPs were 26.09, 59.09, 0.18, and 7.71 µg·mL−1, respectively. The anticancer activity of the IONPs and crude extract was also evaluated. The minimum IC50 values were recorded against MDR 2780AD, i.e., 0.85 (extract) and 0.54 (IONPs). Both of the tested samples were found to be significant (p < 0.001) analgesic and anti-inflammatory. In contrast, the IONPs were found sedative at all tested doses, and the extract showed a significant (p < 0.01) sedative effect at higher doses only.

Analysis of bioactive compounds of hen egg components at the first half of incubation.

A comparative analysis of mass-volume characteristics of structural and morphological components of hen eggs before incubation and on the fifth (HH25-HH27) and 10th (HH36) days of incubation was carried out. During incubation, egg weight decreased by 9.25% (10 days), mainly due to a decrease in albumen weight (35.8%). The ratio of lipid-soluble fraction (LSF) and water-soluble fraction (WSF) in the mixed components and yolk did not change significantly. The total amount of solids in the mixed substances practically does not change during incubation. Antiradical activity of substances increased significantly by more than three times on the fifth day and additionally by 38.6% at the 10th day in relation to the fifth day. Total antioxidant activity increased by 18.9% on the fifth day and by 24.3% on the 10th day, compared to eggs before incubation. Transformation of the main components of WSF and LSF of albumin, yolk, and chicken embryo (CE) was studied using high-performance liquid chromatography and gas chromatography with mass spectrometry. On the 10th day, an increase in the number of high-molecular proteins is recorded, which indicates the activation of enzymatic processes of transformation of the main albumen proteins into proteins of organs and tissues of CE. This may cause an increase in the biological activity of substances. It was found that in conditions of in vitro digestion, antiradical activity increases by two times, anti-inflammatory activity increases by 2.4 times, and an angiotensin-converting enzyme inhibitory effect occurs in the mixed components of a 10-day incubation egg.

Convergent Synthesis, Kinetics, and Computational Studies of Indole(Phenyl)Triazole Bi-Heterocycles Modified With Propanamides as Elastase Inhibitors.

Biological screening combined with the synthesis of heterocyclic compounds with numerous functions is the most effective approach available for pharmacological assessment of potential future medications. In the under taken research that is presented here, 4-(1H-indol-3-yl)butanoic acid was sequentially converted into 4-(1H-indol-3-yl)butanoate, 4-(1H-indol-3-yl)butanohydrazide, and 5-[3-(1H-indol-3-yl)propyl]-1,2,4-triazole-2-thiol as a nucleophile. By treating aryl amines with 3-bromopropanoyl chloride in a series of parallel reactions, different electrophiles were created, leading to the formation of N-(aryl)-3-bromopropanamides. After that, several electrophiles were used in the nucleophilic substitution process of 5 to produce the final bi-heterocyclic derivative. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR, and CHN analysis data. The enzyme inhibitory effects of these bi-heterocyclic propanamides were evaluated against elastase, and all these molecules were identified as potent inhibitors relative to the standard oleanolic acid with IC50 value 13.453±0.015µM used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 9d inhibited elastase competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.51µM. Compound 9d's activity (IC50=0.142±0.014µM) significantly increased when a slightly bulky ethyl group was replaced for the solitary methyl group in 9c at the para-position. However, compound 9e's activity was significantly lower (IC50=38.338±0.993µM) when a more polar ethoxy group was replaced at the same para-position. This was likely because of electronic considerations. These molecules also exhibited mild cytotoxicity toward red blood cell membranes, when analyzing through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds for dealing with the elastase-related ailments such as lung diseases, cyclic neutropenia, pruritic skin disease, and liver infection.

Effects of piperine-haloperidol mixture on ketamine induced schizophrenia rats and metabolism-mediated inhibitory potency: in-vivo and in-vitro evaluation.

Haloperidol, a conventional antipsychotic, wasmixed with piperine in a ketamine-induced schizophrenia rat model to evaluate the interaction potential of this mixture through in-vitro and in-vivo analyses. Piperine, known for its CYP450 enzyme inhibitory effects, enhances the bioavailability of various drugs. Initial in-vitro assays using a high-throughput fluorometric method showed that the haloperidol-piperine mixture inhibited CYP3A4 and CYP2D6 enzymes, comparable to positive controls. In-vivo pharmacokinetic results revealed that piperine significantly increased haloperidol's plasma concentration and area under the curve while reducing clearance, indicating enhanced bioavailability. Pharmacodynamic assessments showed reductions in locomotor activity, immobility time, dopamine levels, and nitric oxide, with increased superoxide dismutase levels in the haloperidol-piperine group compared to haloperidol alone, reflecting enhanced therapeutic efficacy. These findings indicate that piperine can increase haloperidol exposure, potentially allowing for dose reduction and minimizing dose-related side effects. Limitations of this study include reliance on a rat model, which may not fully replicate human metabolism, and lack of long-term safety assessment. Future studies should explore the clinical applicability of this mixture in human trials, particularly focusing on safety, dosage optimization, and long-term effects. Additionally, understanding piperine's role in different metabolic pathways could guide the development of targeted bioavailability enhancers, improving efficacy for a range of CYP450-metabolized medications.

Larvicidal and enzyme inhibition effects of Phoenix pusilla derived Methyl oleate and malathion on Aedes aegypti strains

This study explores the larvicidal potential of methanolic flower extracts from Phoenix pusilla (Pp-Fe), its major compound, and malathion (MLT), against laboratory strain (LS) and field strain (FS) of Aedes aegypti, the dengue mosquito vector. We identified thirty-one derivatives, with methyl oleate (MO) comprising 28.5% of Pp-Fe. Comparative efficacy evaluations were performed using peak dosages of Pp-Fe (500 ppm), MO (5 ppm), and MLT (5 ppm) on LS and FS larvae. Both LS and FS second instars showed higher susceptibility to Pp-Fe (95% and 93%, respectively) and MO (85% and 83%, respectively). MLT resulted in significant mortality rates among LS larvae (98%) and notable reductions among FS larvae (71%). The expression levels of key biomarker enzymes (carboxylesterase, GST, and CYP450) exhibited a consistent decrease and subsequent upregulation in LS and FS larvae following exposure to Pp-Fe and MO, contrasting with the significant expression variations observed in LS and FS larvae exposed to MLT. LS larvae demonstrated heightened susceptibility and evident midgut cell damage following all treatments, suggesting potential disparities in susceptibility and adaptive responses between LS and FS strains towards MLT. These observations underscore the promising larvicidal attributes of Pp-Fe and MO, emphasizing the need for further exploration of their mechanisms of action in the development of environmentally sustainable mosquito control strategies and resistance management.

Sustainable bio-fabrication of Ni/Mn co-doped ZnO nanoparticles using Simarouba glauca leaf extract: Evaluation of non-cytotoxic, anti-carcinogenic, anti-tubercular, anti-bacterial properties, anti-oxidant and hyaluronidase inhibition activities

Metal oxide nanomaterials, notably ZnO NPs, have emerged as pivotal components in various industries due to their exceptional properties. This study focuses on enhancing the bioactive properties of ZnO NPs by co-doping them with Ni and Mn, employing a cost-effective and eco-friendly synthesis method utilizing S. glauca leaf extract as a bio-reductant. Characterization techniques including PXRD, SEM, EDAX, FTIR, and UV–Visible were utilized to analyse the synthesized NPs. The research evaluated the anti-carcinogenic anti-tubercular and anti-bacterial activities. Cytotoxicity of the NPs was examined towards general mammalian cells and yeast cells. Antioxidant activity was determined by Free radical scavenging, Power to reduce ferric ions and inhibition of lipid peroxidation. Also examined the potential of NPs to inhibit the Hyaluronidase enzyme activity, that breaks down Hyaluronic acid and helps in the prognosis of tumour metastasis. Results revealed, significant impacts on these biological processes, highlighting the relevance of our findings for cytotoxicity assessment, therapeutic applications, and biomedical advancements. Results indicated promising potential for Ni and Mn-doped ZnO NPs across various biomedical applications, demonstrating enhanced cytotoxicity against cancer cells, antimicrobial efficacy, antioxidant properties, and enzyme-inhibitory effects. The study concludes that the doped NPs offer versatile functionalities, paving the way for further exploration and development in biomedical and clinical applications, with potential implications for improving healthcare and patient outcomes.

Nanoengineering of Phosphate/Phosphonate Drugs via Competitive Replacement with Metal-Phenolic Networks to Overcome Breast Tumor with Lung and Bone Metastasis.

Phosphate and phosphonate drugs are vital in building organisms, regulating physiological processes, and exhibiting diverse biological activities, including antiviral, antibacterial, antineoplastic, and enzyme-inhibitory effects. However, their therapeutic potential is limited by the lack of advanced nanoengineering technologies. Herein, a competitive coordination strategy for nanoengineering phosphate/phosphonate drugs is introduced. By leveraging the difference in coordination capabilities between polyphenols and phosphates/phosphonates with metal ions, various phosphate/phosphonate-based nanodrugs using metal-phenolic networks (MPNs) as templates and phosphate/phosphonate drugs as competitive agents are constructed. The dynamic nature of these coordination bonds imparts stimuli-responsiveness to the nanodrugs, allowing for targeted release and therapy. As a proof of concept, Fe3+ and galangin are used to form the MPN template, zoledronic acid and cGAMP as competitive agents, and DOX as the loaded drug to construct DOX@Fe-galangin@Fe-zoledronic acid-cGAMP nanodrugs. The results demonstrate that, by triggering pyroptosis and activating the cGAS-STING pathway, the nanodrugs exhibit potent cytotoxicity and accurate selectivity in eradicating orthotopic breast tumors, and activate an antitumor immune response against lung and bone metastases. Because the competitive coordination strategy is applicable to a variety of phosphate/phosphonate agents, it holds significant potential for enhancing the clinical efficacy of phosphate/phosphonate drugs and advancing nanodrug development for complex therapeutic applications.

Studies on the Bioactivity (Antioxidant, Enzyme Inhibitory, Antimicrobial and Cytotoxic) and Chemical Composition of Aqueous Extracts of Some Plant Species Collected from Turkmenistan.

Alhagi persarum (AP), Alhagi persarum flowers (APF), Ephedra equisetina (EE) and Glycyrrhiza glabra root (GGR) have been utilized in Central Asian folk medicine for centuries. In the present study, antioxidant, enzyme inhibition, antimicrobial and cytotoxic effects the aqueous extracts of these plants were studied. In addition, 23 compounds were identified in the extracts using UHPLC-DAD-QqQ-MS/MS analysis. The four plant samples demonstrated promising antioxidant activities in vitro for scavenging of 2, 20-azinobis-(3-ethylbenz-thiazoline-6-sulphonate) radical (ABTS), 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH), and total reducing power. AP (DPPH: 47.39 mg TE/g; ABTS:108.58 mg TE/g; CUPRAC: 117.41 mg TE/g; FRAP: 82.22 mg TE/g) and EE (DPPH: 46.75 mg TE/g; ABTS: 110.51 mg TE/g; CUPRAC: 140.77 mg TE/g; FRAP: 91.00 mg TE/g) displayed the strongest antiradical and reduction abilities in the test system. In terms of enzyme inhibition efficacy, AP and EE showed higher bioactivity. Aqueous extracts demonstrated the most potent efficacy against eight different bacterial and fungal strains in antibacterial (MIC values: 1.5-4 mg/ml) and antifungal (MIC values: 1-8 mg/ml) testing. Contrary to other activities, these aqueous extracts did not show cytotoxic effects against HaCaT cells. All bioactivities suggested that the plants could be utilized as candidate resources in the food and pharmaceutical industries.

White mulberry leaf (Morus alba L.) infusion as a strategy to reduce starch digestibility: The influence of particle size of leaf powder

Mulberry leaf (Morus Alba L.) has been found in clinical trials to be effective in reducing diabetes in Asia. The powdered tea market is expanding in popularity due to its functional properties. This study aimed to examine the influence of different particle sizes of mulberry leaf powder (MLP) infusion on the digestibility of starch in cooked Japonica rice (cv. Koshihikari) and the bioaccessibility of phytochemicals. Dried mulberry leaf was pulverized and sieved into several particle sizes: 160 μm (MLP160), 250 μm (MLP250), 404 μm (MLP404), and 774 μm (MLP774). Through simulated in vitro digestion, we assessed starch hydrolysis (%SH), the kinetics of starch hydrolysis, estimated glycemic index (eGI), as well as total phenolic content (TPC) and total flavonoid content (TFC). The smaller particle size of MLP showed a greater reduction of eGI. Specifically, infusions prepared from MLP160 resulted in a reduction of 15 % in eGI for cooked grains and 3 % for slurries, respectively. The reduction in eGI was attributed to the interaction among flavonoids and digestive enzymes, demonstrating a concentration-dependent manner on enzyme inhibition effect. Pulverization significantly influenced the concentration of phytochemicals and their bioaccessibility in infusions. This study offers valuable insights into determining optimal particle sizes for MLP, considering both physical and functional characteristics as well as implications for the food industry. The results further suggest that MLP infusion holds promise as a functional beverage, potentially providing benefits in reducing postprandial hyperglycemia.

Chemical composition, antioxidant, and enzyme inhibition activities of Crithmum maritimum essential oils: the first chemo-biological study for species grown in North Africa

Crithmum maritimum (sea fennel), is a halophytic plant species found globally in coastal environments. This study is the first investigation into the chemical composition and biological activities of C. maritimum growing wildly in Jebel Akhdar, Libya. Gas Chromatography-Mass Spectrometry (GC-MS) analysis was utilized to identify and profile the plant’s volatile components; it resulted in the identification of twenty-four components, representing 99.17% of the total peaks in the GC-MS chromatogram. The analysis revealed that thymyl methyl ether, γ-terpinene, and ledene oxide, were the major volatile constituents of the plant at relative percentage levels of 56.86, 16.17, and 4.32%, respectively. The analysis also indicated substantial variations in the volatile composition of C. maritimum Libyan species compared to those from various geographic regions. The plant’s volatile oil quality was evaluated by investigating its in vitro antioxidant activity and the oil’s ability to inhibit acetylcholinesterase (AChE) and tyrosinase enzymes. The oil markedly scavenged the free radicals and reduced the ferric ions in the DPPH and FRAP assays at levels of 34.30 ± 0.10 and 38.90 ± 0.51 Trolox equivalents, respectively. The plant’s volatile oil has substantially reduced the AChE at the IC50 value of 34.43 ± 0.25 compared to its effect against tyrosinase (IC50 12.449 ± 0.68). The in silico approach was used to highlight the mechanisms underlying the enzyme inhibitory effect of the plant volatile oil. The stigmastene and γ-santonin demonstrate stronger binding affinity towards AChE and tyrosinase compared to the co-crystalized controls, donepezil and tropolone. The study provides significant information for the environmental changes effect on the volatile constituents of C. maritimum and highlights the plant’s importance within the scope of its antioxidant and enzyme inhibition activities.

Multi-scale structural and In vitro digestion properties of amino acids-tiger nut starch complexes and applications in noodles

Protein and its hydrolysates play crucial roles as nutritional components in daily diets and additives in food processing, their effect on starch digestion attracted extensive attention. In this study, tiger nut starch (TNS) mixed with multiple type of amino acids were subjected to annealing (ANN) treatment. Through the analysis of morphological characteristics, physicochemical properties, molecular structure, and enzyme inhibition effects of these amino acids, the mechanism of diverse in vitro digestion properties of the resulting mixtures were examined. Our findings revealed that the addition of phenylalanine (Phe), lysine (Lys), and histidine (His) significantly reduced rapidly digestible starch (RDS) content while increasing levels of slowly digestible starch (SDS) and resistant starch (RS) content (p<0.05). Phe, Lys, and His were found to influence digestion properties through molecular interactions, as indicated by analyses of relative crystallinity (RC) and short-range order. Notably, Lys and His exhibited notable amylase inhibition effects consequently enhanced enzyme resistance, particularly His on α-amylase (11.98%) and Lys on α-glucosidase (89.33%). Finally, wheat noodles prepared with TNS-Lys and TNS-His showed favorable processing properties and digestion resistant, highlighting their promising applications in low glycemic index foods.

Synthesis of zinc phthalocyanine containing 1,2-phenylene bis(3-chloropropanoate) substituted groups and investigation of their metabolic enzyme inhibitory effects

In this study, 4,5-dicyano-1,2-phenylene dinicotinate compound was obtained as a result of the reaction of 4,5-dichlorophthalonitrile and nicotinic acid. This compound was reacted with the zinc chloride salt to obtain the original zinc phthalocyanine compound bearing 1,2-phenylene bis(3-chloropropanoate) substituted groups. This compound and its starting material were characterized with the assist of 1H NMR, IR, UV–vis, Mass spectrum. In the docking study of compounds (3) and (4) against each target (AChE, BChE, α-Amy and α-Gly), Zn complex (4) exhibits more binding affinity with the target models considered compared to ligand structure (3). Especially, AChE protein and complex (4) form the best binding affinity with a binding energy value of −10.55 kcal/mol. They are compatible and supportive with the data obtained as a result of in vitro analysis. These 4,5-dicyano-1,2-phenylene dinicotinate (3) and 2, 10, 16, 24 – tetrakis 1,2-phenylene bis(3-chloropropanoate) phthalocyaninato) zinc(II) (4) complexes had effective inhibition against α-glucosidase, α-amylase, butyrylcholinesterase and AChE. Also, IC50 amounts were found as 7.84 and 12.36 µM for AChE, 3.80 and 4.56 µM for BChE, 27.08 and 38.14 µM for α-amylase, and 5.30 and 9.73 µM for α-glucosidase.

Review on Therapeutic Diversity of Oxazole Scaffold: An Update

AbstractOxazole, a five‐membered cyclic ring containing oxygen and nitrogen, displays diverse interactions and structural variations, enhancing its potential applications across various domains. Oxazole derivatives exhibit diverse pharmacological activities, including antidiabetic, anticonvulsant, anticancer, phosphodiesterase inhibition, antiprotozoal, and antibacterial effects, making them appealing to medicinal chemists. Their presence in naturally occurring pharmacologically active substances as well as synthetic medicines underscores their therapeutic potential. This review encompasses recent advancements in the biological activities of oxazole derivatives during the period of 2018–2023. The discussed activities include antitumor, central nervous system (CNS) modulation, antidiabetic, anti‐Alzheimer, antibacterial, and enzyme inhibitory effects. The review highlights the mechanisms of action of these compounds in various diseases, the most potent compounds along with their respective IC50/MIC (inhibitory concentration/minimum inhibitory concentration) values, and discusses the models utilized for quantifying their activity. Currently, there are eight FDA‐approved drugs bearing oxazole scaffolds available in the market. Analysis of the literature reveals that the antitumor activity of oxazole derivatives is particularly noteworthy among their various activities. The incorporation of phenyl, methoxyphenyl, or halogen‐substituted phenyl moieties significantly enhances therapeutic activities compared to reference drugs. The substitution flexibility at three positions of oxazole derivatives contributes to their spectrum of pharmacological activities.

Exploring of Chemical Profile and Biological Activities of Three Ocimum Species From Comoros Islands: A Combination of In Vitro and In Silico Insights.

Ocimum species have a great interest in different traditional medicinal systems. This study examined the chemical composition, antioxidant properties, enzyme inhibitory effects, and antibacterial and antifungal activities of the aerial parts of Ocimum gratissimum, Ocimum americanum, and Ocimum basilicum from the Comoros Islands. The extracts were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) to determine their chemical composition. Antioxidant activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), chelating ability, and phosphomolybdenum radical scavenging assays. Enzyme inhibitory activities against acetylcholinesterase (AChE), butrylcholinesterase (BChE), tyrosinase, amylase, and glucosidase were evaluated using spectrophotometric methods. Antibacterial and antifungal activities were tested using the broth microdilution method against selected pathogenic microorganisms. The selected enzymes and proteins were evaluated using in silico methods with biomolecules from these plants. In addition, 111 different metabolites were identified in the tested extracts using advanced HPLC/MS techniques. The most significant number of detected compounds were derivatives of hydroxycinnamic acids, followed by flavonoid glycosides and aglycones and derivatives of hydroxybenzoic acids. All three Ocimum species exhibited significant antioxidant activities, O. gratissimum exhibited the best-reducing abilities in CUPRAC and FRAP assays. In addition, enzyme inhibitory assays revealed that O. americanum had the most potent inhibitory effect on tyrosinase (48.01 ± 3.89 mg kojic acid equivalent [KAE]/g), and amylase (1.08 ± 0.02 mmol acarbose equivalent [ACAE]/g). Antibacterial and antifungal tests demonstrated that the extracts possess broad-spectrum activity. Molecular docking results showed that compounds exhibited remarkable binding energies with target enzymes and proteins. The molecular dynamics simulations identified chicoric acid with MurE of Staphylococcus aureus complex as the most promising drug candidate. These findings support their traditional medical and nutraceutical uses and suggest possibilities for natural functional applications.

Synthesis and anti-Alzheimer activity of new N-(5, 6-dimethyl-1H-benzo[d] imidazol-2-yl)-1-phenylmethanimine derivatives

The cholinesterase group, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), is responsible for inhibiting the actions of choline esters. Benzimidazole derivatives, renowned for their aromatic organic heterocyclic structure, exhibit diverse biological activities, including enzyme inhibitory effects. Imine compounds, easily synthesized, demonstrate notable biological efficacy against various pathogens and enzymes. Synthesize, purify, and characterize novel benzimidazole scaffolds, and evaluate their anti-Alzheimer’s activity by measuring AChE and BChE activities. A new series of benzimidazole phenylmethanimine derivatives (3a–3d) was synthesized through refluxing amine with various benzaldehydes. Products underwent purification by solvent washing and characterization using spectroscopic methods. In vitro anti-Alzheimer’s activity was assessed by measuring inhibitory activity (half-maximal inhibitory concentration [IC50]) against cholinesterase enzymes. the newly synthesized Schiff bases, purified solely by solvent washing, yielded high percentages (81%–91%). These derivatives showed significant inhibitory activity, with low IC50 values observed for compounds 3a and 3d against both enzymes. Molecular docking studies estimated binding energies and identified interacting amino acids in active pockets. Four new derivatives were synthesized with high yields using the classical reflux method. Purification involved solvent washing only, followed by direct spectroscopic analysis. In vitro inhibitory activities against AChE and BChE enzymes were observed, with compounds 3a and 3d showing promising results. Docking studies revealed higher inhibitory activity and lower IC50 values for two derivatives, indicating their potential as potent inhibitors.