Enzyme Inhibition Profile Research Articles

Nizip Yaglık olive leaves (Olea europaea L.) collected at different seasons and altitudes: Enzyme inhibition, antioxidant activities and phenolic compound profiles

Nizip Yaglık olive leaves (Olea europaea L.) collected at different seasons and altitudes: Enzyme inhibition, antioxidant activities and phenolic compound profiles

Unrivalled Insight into Possible Biopharmaceutical Application of Justicia vahlii Roth. (Acanthaceae): Chemodiversity, In Vitro Bioactivities, and Computational Analysis.

Justicia vahliiRoth. is an important wild medicinal food plant traditionally used for treating inflammation and various common ailments. This study investigated the chemical composition, antioxidant, enzyme inhibition and toxicity profiles of n-hexane (nHEJv) and chloroform (CEJv) extracts of J. vahlii. Moreover, the effect of the extracts was evaluated on CCl4 induced liver injury. The total phenolic and flavonoid contents were present in both extracts in significant amount. The UPLC-Q-TOF-MS and GC-MS profiling of CEJv tentatively identified several important phytocompounds. The CEJv extract was comparatively more active for antioxidant activity and α-amylase inhibition, whereas the nHEJv extract presented higher inhibition potential against urease, tyrosinase, and α-glucosidase enzymes. Similarly, the in-silicostudy of four major compounds, i. e., 1-acetoxypinoresinol, 3-hydroxysebacic acid, nortrachelogenin, and viscidulin-III have shown a good docking score against the clinically significant enzymes. The acute oral toxicity and brine shrimp lethality assaysrevealed the extracts as non-toxic. The CCl4 treated animals showed a geared depletion of various antioxidant enzymes which were significantly reversed with the treatment of the extracts. Overall, the study's findings revealed J. vahliiwith antioxidant mediated hepatoprotective and enzyme inhibition potential and warrant further research on isolation of the bioactive compounds.

Heavy metals altered the xenobiotic metabolism of rats by targeting the GST enzyme: An in vitro and in silico study

Among all the heavy metals, Pb, Cd, and As are the most harmful pollutants in the environment. They reach into the organisms via various levels of food chains i.e. air and water. Glutathione-s-transferase (GST, E.C. 2.5.1.18), a key enzyme of xenobiotics metabolism, plays an important role in the removal of several toxicants. The present study aimed to evaluate any inhibitory action of these heavy metals on the GST enzyme isolated from the hepatic tissues of rats. A 10 % (w/v) homogenate of rat liver was prepared in cold and centrifuged at 4 °C at 9000xg for 30 min. The supernatant was collected and kept frozen at −20 °C or used fresh for carrying out different experiments. The activity of GST was monitored spectrophotometrically at 340 nm using 220 μg of soluble protein with varying equal substrate concentrations (0.125–2 mM) in phosphate buffer (50 mM, pH 6.5). To assess the impact of heavy metals on the enzyme activity, different concentrations of Cd (0–0.6 mM) and Pb (0–2 mM) were added to the reaction mixture followed by monitoring the residual activity. The optimum temperature and pH of rat liver GST were found to be 37 °C and 6.5, respectively. The Km value for GST was 0.69 mM and the Vmax was found to be 78.67 U/mg. The Cd and Pb significantly altered the kinetic behaviour of the enzyme. The Vmax and Kcat/Km parameters of GST were recorded to be decreased after interaction with Cd and Pb individually and showed a mixed type of inhibition pattern suggesting that these inhibitors may have a greater binding affinity either for the free enzyme or the substrate-enzyme complex. These metals showed a time-dependent enzyme inhibition profile. Cd was found to be the most potent inhibitor when compared to other treated metals; the order of inhibitory effect of metal ions was Cd>Pb>As. The in silico ion docking analysis for determining the probable interactions of Cd and Pb with fragmented GST validated that Cd exhibited higher inhibition potential for the enzyme as compared to Pb. The results of the present study indicated that exposure of both the Cd and Pb may cause significant inhibition of hepatic GST; the former with higher inhibitory potential than the later. However, As proved to be least effective against the enzyme under the aforesaid experimental conditions.

An evaluation of the antioxidant potential and in vitro enzyme inhibition profile of selected bryophytes from Northeast Anatolia (Türkiye)

Interest in the use of bryophytes in pharmaceutical, cosmetic, and food industrial applications is growing worldwide due to their secondary metabolites. In this study, n-hexane crude extracts and further fractions (aqueous, ethyl acetate and n-butanol) of aqueous ethanol (80:20, ethanol:H2O, v/v) were obtained from five different bryophytes (Pellia epiphylla, Conocephalum conicum, Porella platyphylla, Plagiomnium cuspidatum and Mnium spinulosum) collected from Trabzon, Türkiye. The total phenolic compound (TPC) content, antioxidant capacity (AC) and enzyme inhibition activity (acetylcholine esterase, butyrylcholine esterase, tyrosinase, α-amylase and α-glucosidase) of the extracts and fractions were species-specific and varied significantly between the crude extracts and fractions. Among the different bryophytes, Porella platyphylla and Pellia epiphylla in n-butanol and Plagiomnium cuspidatum and Mnium spinulosum in ethyl acetate fraction exhibited the highest TPC contents and AC values. The contents of phenolic acids liberated in free, ester and glycoside forms were also species-specific. p-Hydroxybenzoic acid (p-HBA) in free form in P. cuspidatum and P. platyphylla, p-coumaric acid (p-CoA) in ester form and m-hydroxybenzoic acid (m-HBA) in glycoside form in M. spinulosum were the major phenolic acids in the bryophytes. The n-hexane extracts of the bryophytes, in particular M. spinulosum, had IC50 values ​​almost 100 times lower than acarbose. This suggests that M. spinulosum in particular may represent a possible candidate for the production of new antidiabetic agents. Communicated by Ramaswamy H. Sarma

Novel Mitochondrial and DNA Damaging Fluorescent Calix[4]arenes Bearing Isatin Groups as Aromatase Inhibitors: Design, Synthesis and Anticancer Activity

Breast cancer causes a high rate of mortality all over the world. Therefore, the present study focuses on the anticancer activity of new lower rim-functionalized calix[4]arenes integrated with isatin and the p-position of calixarenes with 1,4-dimethylpyridinium iodine against various human cancer cells such as MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the PNT1A healthy epithelial cell line. It was observed that compound 6c had the lowest values in MCF-7 (8.83 µM) and MDA-MB-231 (3.32 µM). Cell imaging and apoptotic activity studies were performed using confocal microscopy and flow cytometry, respectively. The confocal imaging studies with 6c showed that the compound easily entered the cell, and it was observed that 6c accumulated in the mitochondria.The Comet assay test was used to detect DNA damage of compounds in cells. It was found that treated cells had abnormal tail nuclei and damaged DNA structures compared with untreated cells. In vitro human aromatase enzyme inhibition profiles showed that compound 6c had a remarkable inhibitory effect on aromatase. Compound 6c displayed a significant inhibition capacity on aromatase enzyme with the IC50 value of 0.104 ± 0.004 µM. Thus, not only the anticancer activity of the new fluorescent derivatives, which are the subject of this study, but the aromatase inhibitory profiles have also been proven.

Phenolic Compounds of Phlomis tuberosa by LC–MS/MS‐Determination of Antioxidant Activity, Molecular Docking, and Enzyme Inhibition Profiles

AbstractPhlomis species have traditionally been employed for the treatment of a number of ailments such as influenza, the common cold, asthma, bronchitis, coughs, hemorrhoids, ulcers, and gastrointestinal disorders. The goal of this study is to compare the anti‐diabetic, anti‐glaucoma, and anti‐Alzheimer's properties and antioxidant activities of methanol (MEPT) and aqueous (WEPT) extracts from the aerial part of P. tuberosa L. Tandem mass spectrometry and liquid chromatography (LC–MS/MS) were used to investigate the compounds of MEPT and WEPT. The inhibitory effects of MEPT and WEPT on the enzymes acetylcholinesterase (AChE), carbonic anhydrase II (CA II) and α‐glycosidase were investigated and molecular docking studies demonstrated binding interactions between the major compounds chlorogenic acid, cyanidin‐3‐O‐glycoside, quinic acid, rosmarinic acid with AChE, CA II and α‐glycosidase enzymes. In addition to that, the total content of phenols and flavonoids was analyzed. Furthermore, the antioxidant activity was evaluated by DPPH, ABTS, DMPD, ferrous ions (Fe2+) chelating, FRAP, CUPRAC, and ferric ions (Fe3+) reducing methods. This study is the first of its kind to show that MEPT and WEPT possess inhibitory effects on AChE, CA II and α‐glycosidase, as well as displaying antioxidant properties.

The relationship between the chemical components and skin-related enzyme inhibition, antioxidant activities and toxicity profile of Helichrysum armenium subsp. armenium

The aerial parts of Helichrysum armenium subsp. armenium were subjected to methanol, ethyl acetate and n-hexane extraction. The extracts were evaluated for their in vitro enzyme inhibitory activity [lipoxygenase (LOX), tyrosinase and elastase], antioxidant activity and toxicity (on fibroblast cells). All the extracts displayed a weak effect on LOX and elastase. The ethyl acetate extract showed the highest inhibition on tyrosinase enzyme with IC50 = 460 µg/mL, while kojic acid had IC50 = 30 µg/mL. The methanol and ethyl acetate extracts compared to the n-hexane extract exhibited stronger DPPH• and ABTS•+ scavenging activity, as well as iron(II)-chelating potential, and were shown to have rich phenolic and flavonoid contents. The methanol extract was toxic to healthy fibroblast cells at a higher concentration with IC50 > 500 µg/mL compared to the other extracts. Phytochemical analysis of the extracts was made quantitatively by LC–MS/MS. The major components identified in the methanol and the ethyl acetate extracts were astragalin, quinic acid, apigenin-7-glycoside, isoquercitrin, chlorogenic acid, naringenin, apigenin and luteolin-7-glucoside. The compounds detected in the n-hexane extract were much fewer. Based on these findings, H. armenium subsp. armenium can be considered to be a natural raw material with the potential to be used in the cosmetic industry.

Harnessing the Bioactive Potential of Limonium spathulatum (Desf.) Kuntze: Insights into Enzyme Inhibition and Phytochemical Profile.

This study assessed the halophyte species Limonium spathulatum (Desf.) as a possible source of natural ingredients with the capacity to inhibit enzymes related to relevant human health disorders and food browning. Extracts using food-grade solvents such as water and ethanol were prepared by maceration from dried L. spathulatum leaves. They were evaluated for in vitro inhibition activity of enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), α-glucosidase, tyrosinase and lipase, related to Alzheimer's disease, type-2-diabetes mellitus, skin hyperpigmentation, and obesity, respectively. These extracts were also appraised for in vitro acute toxicity on tumoral and non-tumoral cell lines and their chemical composition by high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS). The extracts were more effective towards BChE than AChE. The best results were obtained with the hydroethanolic and water extracts, with IC50 values of 0.03 mg/mL and 0.06 mg/mL, respectively. The hydroethanolic extract had the highest capacity to inhibit α-glucosidase (IC50: 0.04 mg/mL), higher than the positive control used (acarbose, IC50 = 3.14 mg/mL). The ethanol extract displayed the best inhibitory activity against tyrosinase (IC50 = 0.34 mg/mL). The tested samples did not inhibit lipase and exhibited low to moderate cytotoxic activity against the tested cell lines. The hydroethanolic extract had a higher diversity of compounds, followed by the ethanol and water samples. Similar molecules were identified in all the extracts and were mainly hydroxybenzoic acids, hydroxycinnamic acids, and flavonoids. Taken together, these results suggest that L. spathulatum should be further explored as a source of bioactive ingredients for the food, cosmetic, and pharmaceutical industries.

Antioxidant, Antiglaucoma, Anticholinergic, and Antidiabetic Effects of Kiwifruit (Actinidia deliciosa) Oil: Metabolite Profile Analysis Using LC-HR/MS, GC/MS and GC-FID.

Determining the antioxidant abilities and enzyme inhibition profiles of medicinally important plants and their oils is of great importance for a healthy life and the treatment of some common global diseases. Kiwifruit (Actinidia deliciosa) oil was examined and researched using several bioanalytical methods comprehensively for the first time in this research to determine its antioxidant, antiglaucoma, antidiabetic and anti-Alzheimer's capabilities. Additionally, the kiwifruit oil inhibitory effects on acetylcholinesterase (AChE), carbonic anhydrase II (CA II), and α-amylase, which are linked to a number of metabolic illnesses, were established. Furthermore, LC-HRMS analysis was used to assess the phenolic content of kiwifruit oil. It came to light that kiwifruit oil contained 26 different phenolic compounds. According to the LC-HRMS findings, kiwifruit oil is abundant in apigenin (74.24 mg/L oil), epigallocatechin (12.89 mg/L oil), caryophyllene oxide (12.89 mg/L oil), and luteolin (5.49 mg/L oil). In addition, GC-MS and GC-FID studies were used to ascertain the quantity and chemical composition of the essential oils contained in kiwifruit oil. Squalene (53.04%), linoleoyl chloride (20.28%), linoleic acid (2.67%), and palmitic acid (1.54%) were the most abundant compounds in kiwifruit oil. For radical scavenging activities of kiwifruit oil, 1,1-diphenyl-2-picryl-hydrazil (DPPH•) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) radicals scavenging techniques were examined. These methods effectively demonstrated the potent radical scavenging properties of kiwifruit oil (IC50: 48.55 μg/mL for DPPH•, and IC50: 77.00 μg/mL for ABTS•+ scavenging). Also, for reducing capabilities, iron (Fe3+), copper (Cu2+), and Fe3+-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) reducing abilities were studied. Moreover, kiwifruit oil showed a considerable inhibition effect towards hCA II (IC50: 505.83 μg/mL), AChE (IC50: 12.80 μg/mL), and α-amylase (IC50: 421.02 μg/mL). The results revealed that the use of kiwifruit oil in a pharmaceutical procedure has very important effects due to its antioxidant, anti-Alzheimer, antidiabetic, and antiglaucoma effects.

Structure-guided design and development of vanillin-triazole conjugates as potential MARK4 inhibitors targeting hepatocellular carcinoma

Microtubule affinity-regulating kinase 4 (MARK4) is a potential therapeutic target for cancer therapy, as it plays a crucial role in cell division and metastasis. Vanillin is an essential ingredient of vanilla bean extract and has several pharmacological activities, including high inhibitory potential for MARK4. This study aimed to synthesize vanillin-triazole derivatives to develop MARK4-specific inhibitors. We employed experimental and computational approaches to investigate the potentials of synthesized vanillin-triazoles (5a–q) for inhibiting MARK4 activity and subsequent growth of hepatocellular carcinoma (HCC) cells (C3A/HepG2 and SNU-475). In addition, molecular docking and MD simulation studies suggest that vanillin-triazoles bind strongly with the active site residues of MARK4 and are stabilized by numerous non-covalent interactions. Among all 5a, 5g, 5h, and 5j showed an appreciable enzyme inhibition profile and strong binding affinities with MARK4 in the sub-micromolar range. Moreover the compound 5g suppresses the cell proliferation and migration potential of C3A and SNU-475 cells and strongly induces apoptosis. The present study suggests that vanillin-triazole (5g) has high inhibitory activity towards MARK4 and could be utilized for developing MARK4-based anticancer therapies.

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Comprehensive Metabolite Profiling of Cinnamon (Cinnamomum zeylanicum) Leaf Oil Using LC-HR/MS, GC/MS, and GC-FID: Determination of Antiglaucoma, Antioxidant, Anticholinergic, and Antidiabetic Profiles.

In this study, for the first time, the antioxidant and antidiabetic properties of the essential oil from cinnamon (Cinnamomum zeylanicum) leaves were evaluated and investigated using various bioanalytical methods. In addition, the inhibitory effects of cinnamon oil on carbonic anhydrase II (hCA II), acetylcholinesterase (AChE), and α-amylase, which are associated with various metabolic diseases, were determined. Further, the phenolic contents of the essential oil were determined using LC-HRMS chromatography. Twenty-seven phenolic molecules were detected in cinnamon oil. Moreover, the amount and chemical profile of the essential oils present in cinnamon oil was determined using GC/MS and GC-FID analyses. (E)-cinnamaldehyde (72.98%), benzyl benzoate (4.01%), and trans-Cinnamyl acetate (3.36%) were the most common essential oils in cinnamon leaf oil. The radical scavenging activities of cinnamon oil were investigated using 1,1-diphenyl-2-picryl-hydrazil (DPPH•), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and (ABTS•+) bioanalytical scavenging methods, which revealed its strong radical scavenging abilities (DPPH•, IC50: 4.78 μg/mL; and ABTS•+, IC50: 5.21 μg/mL). Similarly, the reducing capacities for iron (Fe3+), copper (Cu2+), and Fe3+-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) were investigated. Cinnamon oil also exhibited highly effective inhibition against hCA II (IC50: 243.24 μg/mL), AChE (IC50: 16.03 μg/mL), and α-amylase (IC50: 7.54μg/mL). This multidisciplinary study will be useful and pave the way for further studies for the determination of antioxidant properties and enzyme inhibition profiles of medically and industrially important plants and their oils.

Design, Synthesis, Kinetic Analysis and Pharmacophore-Directed Discovery of 3-Ethylaniline Hybrid Imino-Thiazolidinone as Potential Inhibitor of Carbonic Anhydrase II: An Emerging Biological Target for Treatment of Cancer.

Carbonic anhydrases (CA), having Zn2+ metal atoms, are responsible for the catalysis of CO2 and water to bicarbonate and protons. Any abnormality in the functioning of these enzymes may lead to morbidities such as glaucoma and different types of cancers including brain, renal and pancreatic carcinomas. To cope with the lack of presence of a promising therapeutic agent against these cancers, searching for an efficient and suitable carbonic anhydrase inhibitor is crucial. In the current study, ten novel 3-ethylaniline hybrid imino-thiazolidinones were synthesized and characterized by FTIR, NMR (1H, 13C), and mass spectrometry. Synthesis was carried out by diethyl but-2-ynedioate cyclization and different acyl thiourea substitutions of 3-ethyl amine. The CA (II) enzyme inhibition profile for all synthesized derivatives was determined. It was observed that compound 6e demonstrated highest inhibition of CA-II with an IC50 value of 1.545 ± 0.016 µM. In order to explore the pharmacophoric properties and develop structure activity relationship, in silico screening was performed. In silico investigations included density functional theory (DFT) studies, pharmacophore-guided model development, molecular docking, molecular dynamic (MD) simulations, and prediction of drug likeness scores. DFT investigations provided insight into the electronic characteristics of compounds, while molecular docking determined the binding orientation of derivatives within the CA-II active site. Compounds 6a, 6e, and 6g had a reactive profile and generated stable protein-ligand interactions with respective docking scores of -6.12, -6.99, and -6.76 kcal/mol. MD simulations were used to evaluate the stability of the top-ranked complex. In addition, pharmacophore-guided modeling demonstrated that compound 6e produced the best pharmacophore model (HHAAARR) compared to standard brinzolamide. In vitro and in silico investigations anticipated that compound 6e would be an inhibitor of carbonic anhydrase II with high efficacy. Compound 6e may serve as a potential lead for future synthesis that can be investigated at the molecular level, and additional in vivo studies are strongly encouraged.

Investigation of antioxidant activity and antiurease, anticollagenase enzyme inhibition profile of oleaster seeds

In this study, the inhibitory effects of extracts prepared from oleaster seeds on antioxidant activity, anti-urease and anti-collagenase enzyme activities, which have an important area in health, were investigated. For this purpose, the inhibitory effects of aqueous and methanolic extracts of these oleaster seeds on these enzymes were analyzed by spectrophotometric measurements. The inhibitory effect of the prepared extracts on these enzymes was evaluated by in vitro method. Only the aqueous extract was found to show both anti-urease and anti-collagenase activity. It was determined that it showed higher inhibition activity than the urease standard. Accordingly, the anti-urease IC50 value of the extract was 0.23 ± 0.003μg/mL; the % inhibition value at 2.8 µg/mL extract concentration was determined as 36.54 ± 1.11. Anti-collagenase IC50 value 2.8±1.12 μg/mL; the % inhibition value at 4.6 µg/mL extract concentration was determined as 50.7±0.01. The IC50 value of epigallocatechingallate anti-collagenase, which is the anti-collagenase standard, was determined as 1.05±0.002 μg/mL. DPPH and ABTS methods were used to examine the antioxidant activities of oleaster seeds extracts. According to DPPH results, while aqueous extract provided 25,85 % removal, the methanolic extract provided 20,44 % removal. In ABTS removal activity, while aqueous extract provided 25,55 % removal, the methanolic extract provided 18,23% removal. This study clearly shows that oleaster seeds the aqueous extract of can be used as an alternative source of anti-urease and anti-collagenase source. Due to the important role of these enzymes in various diseases, new drugs with inducing or inhibitory effects should be developed.

Exploring enzyme inhibition profiles of novel halogenated chalcone derivatives on some metabolic enzymes: Synthesis, characterization and molecular modeling studies

Enzyme inhibition is a very active area of research in drug design and development. Chalcone derivatives have a broad enzyme inhibitory activity and function as potential molecules in the development of new drugs. In this study, the synthesized novel halogenated chalcones with bromobenzyl and methoxyphenyl moieties were evaluated toward the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes. They showed highly potent inhibition ability toward AChE with Ki values of 1.83 ± 0.21–11.19 ± 0.96 nM and BChE with Ki values of 3.35 ± 0.91–26.70 ± 4.26 nM; hCA I with Ki values of 29.41 ± 3.14–57.63 ± 4.95 nM, and hCA II with Ki values of 24.00 ± 5.39–54.74 ± 1.65 nM. Among the tested enzyme inhibitions, compounds 14 and 13 were the most active compounds against AChE and BChE. Docking studies were performed to the most active compounds against AChE, BChE, hCA I and hCA II to propose a binding mode in the active site and molecular dynamics simulations were studied to check the molecular interactions and the stability of the ligands in the active site. The results may contribute to the development of new drugs particularly to treat some global disorders including Alzheimer’s disease (AD), glaucoma, and diabetes.

Synthesis, characterization, antibacterial, antioxidant activity, and lipoxygenase enzyme inhibition profile of silver nanoparticles (AgNPs) by green synthesis from Seseli resinosum Freyn & Sint

In the study, silver nanoparticles (AgNPs) were successfully synthesized by an environmentally friendly synthesis method using Seseli resinosum Freyn & Sint extract. The synthesized silver nanoparticles were characterized by ultraviolet/visible light absorption spectrophotometer (UV-Vis), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analysis. As a result of the characterization, it was determined that 33 nm spherical nanoparticles were formed, showing a spectrum at 420 nm wavelength. Silver nanoparticles showed a bacteriocidal effect against all bacterial strains. DPPH and ABTS methods were used to examine the antioxidant activities of plant extracts and AgNPs. In DPPH removal activity, AgNPs obtained by green synthesis provided a high rate of inhibition removal compared to the extract. According to this percentage, while silver nanoparticles provided 22% removal, the extract provided 15% removal. In ABTS removal activity, when AgNPs were obtained by green synthesis compared to the extract, silver nanoparticles provided 25% removal, while the extract provided 18% removal. The characterization of silver nanoparticles synthesized by the green synthesis method and their antioxidant activity were investigated, and the obtained values indicate the presence of an antioxidant capacity. In addition, the inhibitory effects of the extract and AgNP on lipoxygenase activity, which has an important place in health, were investigated. It was determined that the aqueous extract of S. resinosum and the AgNP synthesized from the extract had lipoxygenase enzyme inhibitory activity.

Polyphenol Contents, Potential Antioxidant, Anticholinergic and Antidiabetic Properties of Mountain Mint (Cyclotrichium leucotrichum).

In the present work, antioxidant and antidiabetic potentials of mountain mint [Cyclotrichium leu-cotrichum (Stapf ex Rech. Fil.) Leblebici] was the first time appraised. In this sense, methanol (MECL) and water (WECL) extracts were obtained from aerial parts of mountain mint (Cyclotrichium leucotrichum) and studied for their antioxidant ability by several bioanalytical assays. Also, their inhibition profiles were realized toward several metabolic enzymes connected to some diseases, including butyrylcholinesterase (BChE), α-glycosidase, acetylcholinesterase (AChE), and α-amylase enzymes. Additionally, their phenolic contents were determined by putative chromatographic method of LC/MS/MS. Consequently, nineteen phenolic molecules were identified in MECL and fifteen phenolic molecules were found in WECL. Also, antioxidant effects of both extracts were studied using by the methods of 1,1-diphenyl-2-picryl-hydrazyl (DPPH⋅), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+ ) and N,N-dimethyl-p-phenylenediamine (DMPD.+ ) scavenging activities, ferric (Fe3+ ) and cupric (Cu2+ ) ions and Fe3+ -2,4,6-tri(2-pyridyl)-s-triazine (TPTZ) reducing capacities. MECL and WECL were found as powerful DPPH⋅ (IC50 : 23.74 and 28.85 μg/mL), ABTS.+ (IC50 : 12.53 and 14.05 μg/mL) and DMPD.+ scavenging effects (IC50 : 43.52 and 54.80 μg/mL). Also, both extracts demonstrated the effective inhibition on AChE (IC50 : 69.31 and 115.51 μg/mL), BChE (IC50 : 57.75 and 86.62 μg/mL), α-glycosidase (IC50 : 36.47 and 62.94 μg/mL) and α-amylase (IC50 : 1.01 and 3.43 μg/mL). This study will be useful for future studies to determine the antioxidant properties and enzyme inhibition profile of food, medical and industrially important plants.

HCIP: An Online database for prediction CYP450 Enzyme Inhibition potential of bioactive compounds

Background: Concomitant administration of herbal medicine and conventional may lead to severe metabolism-oriented herb-drug interactions. However, detecting herb-drug interaction is expensive and higher time-consuming. Several computer-aided techniques have been proposed in recent years to predict drug interactions. However, most of the methods cannot predict herb-drug interactions effectively.
 Methods: Canonical SMILES of bioactive compounds was gathered from the PubChem online database, and its inhibition details were gathered PKCSM from the webserver.
 Results: By searching the bioactive compound name in the search bar of “The Herb-CYP450 Enzyme Inhibition Predictor online database” (HCIP- http://hcip.in/), it will provide the liver enzyme inhibition profile of the selected bioactive compound. For example; Guggulsterone: CYP3A4 inhibitor. 
 Conclusion: The Herb-CYP450 Enzyme Inhibition Predictor online database is very peculiar and easy to determine the inhibition profile of the targeted bioactive compound.
 Keywords: CYP450; Enzyme inhibition; Bioactive Compounds; Online database; Herb-Drug Interaction

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile.

Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.

Chemical profiling and pharmaco-toxicological activity of Origanum sipyleum extracts: Exploring for novel sources for potential therapeutic agents.

The phytochemical, antiradical, and enzyme inhibition profile of three solvent extracts (ethyl acetate, methanol, water) of Origanum sipyleum were assessed. We also performed a pharmacological study in order to explore protective effects induced by extracts in inflamed colon. LC-MS analysis revealed that the extracts contained different classes of phenolics. The aqueous extract showed the highest antioxidant and acetylcholinesterase (AChE) inhibitory effects. Total phenol and flavonoid contents were highest in aqueous and ethyl acetate extract, respectively. All extracts were effective in reducing colon pro-oxidant and pro-inflammatory biomarkers. The extracts revealed also able to inhibit fungal and bacterial species involved in ulcerative colitis, including Candida albicans, Candida tropicalis, Staphylococcus aureus, and Staphylococcus thyphimurium. Finally, we also showed the antiproliferative effects exerted by the EA extracts on human colon cancer HCT116 cell line. Concluding, our results indicated that O. sipyleum extracts displayed promising therapeutic properties which warrants further validation. PRACTICAL APPLICATIONS: The present phytochemical and biological studies, including antioxidant, anti-inflammatory, and antimicrobic assessments, showed significant protective effects exerted by O. sipyleum extracts in an experimental model of ulcerative colitis. The results are intriguing and suggest potential applications O. sipyleum extracts as sources of natural agents for the management of clinical symptoms related to ulcerative colitis, characterized by increased burden of oxidative stress and microbiome dysbiosis.