Publications

Determination of antioxidant, DNA protection, enzyme inhibition potential and molecular docking studies of a biomarker ursolic acid in <i>Nepeta species</i>

Ursolic acid (UA), which has many biological properties such as anti-cancer, anti-inflammatory and antioxidant, and regulates some pharmacological processes, has been isolated from the flowers, leaves, berries and fruits of many plant species. In this work, UA was purified from the methanol-chloroform crude extract of Nepeta species (N. aristata, N. baytopii, N. italica, N. trachonitica, N. stenantha) using a silica gel column with chloroform or ethyl acetate solvents via bioactivity-guided isolation. The most active sub-fractions were determined under bioactivities using antioxidant and DNA protection activities and enzyme inhibitions. UA was purified from these fractions and its structure was elucidated by NMR spectroscopy techniques. The highest amount of UA was found in N. stenantha (8.53 mg UA/g), while the lowest amount of UA was found in N. trachonitica (1.92 mg UA/g). The bioactivities of UA were evaluated with antioxidant and DNA protection activities, enzyme inhibitions, kinetics and interactions. The inhibition values (IC50) of α-amylase, α-glucosidase, urease, CA, tyrosinase, lipase, AChE, and BChE were determined between 5.08 and 181.96 µM. In contrast, Ki values of enzyme inhibition kinetics were observed between 0.04 and 0.20 mM. In addition, Ki values of these enzymes for enzyme-UA interactions were calculated as 0.38, 0.86, 0.45, 1.01, 0.23, 0.41, 0.01 and 2.24 µM, respectively. It is supported that UA can be widely used as a good antioxidant against oxidative damage, an effective DNA protector against genetic diseases, and a suitable inhibitor for metabolizing enzymes.Communicated by Ramaswamy H. Sarma

Synthesis, spectral characterization and biological activities of o,o'-dihydroxyazo compounds containing gallic acid: Molecular docking and dynamics simulation and MM-PBSA studies

Nepetanudoside B, a potential new food additive isolated from Nepeta aristata: antioxidant, antibacterial, DFT, ADME/T, PASS prediction and MTT analysis studies

Antibacterial and Antioxidant Molecule Isolated from Nepeta aristata Boiss Et Kotschy Ex Boiss plant: 1,5,9-Epideoxyloganic Acid

1,5,9-Epideoxyloganic acid (ELA) was isolated from the methanol fraction of endemic Nepeta aristata crude methanol-chloroform by chromatographic methods (preparative-HPLC, silica, and sephadex column). The structure of ELA was determined with 1H NMR and 13C NMR spectrometry. Furthermore, the mass of the molecule was confirmed by mass spectrometry. ELA's antioxidant and antibacterial activities were examined and also compared to standards. ELA exhibited the best antibacterial activity with inhibition zone against K. pneumoniae (11.50 mm), S. aureus (10.00 mm), and also effective minimum inhibition concentration value against E. faecalis (8 µg/mL). The antioxidant properties of ELA were assessed with posphomolybdenium reducing, reducing power, metal chelating, H2O2, DPPH˙, ABTS˙⁺, and O2˙ˉ scavenging activities. The posphomolybdenium, O2˙ˉ, and H2O2 scavenging activities of ELA were found effective at 136.02±3.99, 3.54±0.26 and 9.67±1.26 µg/mL, respectively. As a result, the effective antioxidant and antimicrobial activity values of the ELA molecule may be a source that can be used in pharmacology in the future.

Synthesis, Spectral Characterization, Biological Activities, Enzyme Inhibition and Molecular Docking Studies of O,O'-Dihydroxyazo Compounds Containing Gallic Acid

Synthesis, characterization, antioxidant, and antibacterial activities of new 2,3-dimethoxy and 3-acetoxy-2-methyl benzamides

Cytotoxicity of <i>Dysphania botrys</i> L. Extracts Against HEPG2 and SAOS‐2, In Vitro and In Silico

ABSTRACT Cancer is a leading cause of mortality worldwide, and plants natural products are known to be safer sources of anticancer agents. Dysphania botrys , is a plant traditionally used against gastrointestinal infections, anti‐inflammatory purposes and as spice. This study was designed to investigate the anticancer potential of D. botrys . The hexane and methanol–chloroform extracts were prepared by maceration of the crushed air‐dried plant material sequentially in the solvents. GC–MS/MS and LC–ESI–MS/MS were used to identify phytochemical constituents in the extracts and their antiproliferative properties were assessed against liver (HEPG2) and bone (SAOS‐2) cancer cell lines by MTT assay. Endothelial HUVEC cells were used to assess selectivity and cytotoxicity. In addition, in silico methods such as DFT, MEP, molecular docking, MD and MM–PBSA were performed on major compounds. In the GC–MS/MS analysis, palmitic, linoleic, oleic and stearic acids were detected in the hexane extract, while LC–ESI–MS/MS analysis revealed that the methanol–chloroform extract was rich in phenolic and polyphenolic compounds, including trans ‐ferulic acid, vanillic acid, sinapic acid, trans ‐cinnamic acid and resveratrol as the major components. MTT assay demonstrated time‐dependent antiproliferative effects of both extracts. The methanol–chloroform extract exhibited notable IC 50 values: 39.30–14.56 (24–48 h, HEPG2); 61.96–28.32 (24–48 h, SAOS‐2), and no cytotoxicity was observed up to 93.09 µg/mL on HUVEC (normal cells). The IC 50 values were comparable to those of the reference drug 5‐fluorouracil, but with significantly reduced toxicity towards normal cells. According to the results of molecular docking, resveratrol was identified as the most effective antiproliferative molecule, and this was confirmed by MD and MM–PBSA. Therefore, D. botrys is a potential source of anticancer phytomedicine against liver and bone cancer that requires further investigations.

Antibacterial flavonoids from Tetrapleura tetraptera (Fabaceae) fruit pulp, in silico studies

Urease inhibitory potency of Chenopodium quinoa seed extract: LC–ESI–MS/MS, GC–MS/MS analysis, biological evaluations, molecular docking, ADMET property, DFT calculation and PASS prediction

Phenolic profile, antioxidant, DNA protection, acetylcholinesterase, butyrylcholinesterase and urease inhibition activities of Coriandrum sativum L. leaf, seed and flower extracts

In this study, chemical content, antioxidant activities, enzyme inhibition activities, and DNA protection activities of extracts obtained from different solvents of the Coriandrum sativum leaf, flower and seed were determined. Total phenol and flavonoid contents of C. sativum leaf, seed and flower hexane extracts were higher than water, methanol, ethanol and ethyl acetate extracts. The highest anthocyanin content was found in the flower part of C. sativum. From the antioxidant activity tests, total antioxidant activity of flower aqueous extract, reducing power of seed aqueous extract, H2O2 scavenging activity of leaf ethyl acetate extract, OH˙ radical scavenging activity of leaf hexane extract, free radical scavenging activity of flower methanol extract, metal chelate activity of leaf ethyl acetate extract, superoxide anion scavenging activity of leaf aqueous extract and lipid peroxidation inhibition activity of the leaf ethyl acetate extract had the highest. It was found that the urease inhibition activity of the seed methanol extract and the acetylcholinesterase and butyrylcholinesterase inhibition activities of the seed ethanol extract presented effective inhibition activity as 80.30±0.20%, 112.83±10.75 µg/mL, and 334.28±23.09 µg/mL, respectively. The leaf hexane, flower ethyl acetate, and leaf methanol extracts showed the highest DNA protection activities with values of 71.86%, 70.89%, and 69.38%, respectively. According to the phytochemical content and biochemical activity results, this study is a valuable report proving that the C. sativum plant is a natural effective product.

Preparation, structural analysis, bioactivity assessment, enzyme and molecular docking calculations of some furan/thiophene-2-carboxamide derivatives

<i>In Vitro</i> Bioactivities and <i>In Silico</i> ADME Profile for Potential Biological Target Prediction of Selected Phytochemicals Using Six <i>Nepeta</i> Species

Abstract Several Nepeta species, used in traditional uses, represent sources of valuable phytochemical composition, as well as in vitro biological and in silico clinical activities. In the present study, the antioxidant and DNA protective properties of methanol: chloroform (1 : 1) extracts of six Nepeta species were evaluated by comparison with standards. In HPLC‐MS/MS analysis, the main components of the extracts were identified as rosmarinic acid, caffeic acid, chlorogenic acid, shikimic acid, and scutellarin. In the GC‐FID analysis, the highest components were palmitate and cis ‐11‐eicosenoic acid. N. aristata has the greatest total phenol and flavonoid contents. N. baytopii, N. aristata, N. italica, N. stenantha , and N. nuda exhibited the highest antioxidant activities. The N. nuda, N. aristata, N. italica , and N. trachonitica extracts were shown to have the most potent DNA protection activity. According to the result of the GC‐FID and HPLC‐MS/MS analysis of Nepeta extracts, ADMET studies of the main components of the extracts were performed. It was evaluated that palmitic acid had BBB permeability, but oleic acid was toxic. The in vitro and in silico results confirmed that Nepeta L. extracts are potential natural products.

Extracts and silver nanoparticles from different parts of Rheum ribes: Characterization, in vitro antibacterial, and antioxidant activities, and in silico molecular dynamics studies

Rheum ribes is a medicinal plant with antioxidant, antibacterial effects, which have been demonstrated in various studies. In this study, the biological activities (antioxidant and antimicrobial) and phytochemical contents (total phenolic content and phenolic substances content by LC-ESI-MS/MS) of the fruit and peel extracts obtained from R. ribes were determined. The antioxidant content (DPPH˙ and FRAP) and total phenolic content (FCR) of R. ribes were analyzed for the first time using a new potentiometric biosensor method. In addition, the characteristic properties (XRD, FT-IR, FE-SEM, FESEM-EDX, TEM, and UV-Vis) and antibacterial properties of silver nanoparticles (AgNPs) prepared by an environmentally friendly green synthesis method were investigated. In addition, the interactions of the main component (hesperidin) in the LC-ESI-MS/MS content analyses with the topoisomerase IV were calculated theoretically. While the antioxidant activity of the R. ribes peel extract was comparable to that of the fruit extract, it was higher for FRAP and DPPH˙ scavenging activity. R. ribes (fruit)-AgNPs were found to have high activity against the microorganisms. The MolDock scores of hesperidin and possible hesperidin-AgNP were calculated to be -111.83 and -171.08, respectively. Thus, hesperidin-AgNP complex was found to have higher inhibitory properties than hesperidin. In the 100-ns MD simulation, the RMSD values were constant at 10 nm and the MM/PBSA calculation resulted in a binding energy of -16.15 kcal/mol for hesperidin.

Phytochemical profiling, molecular docking and ADMET prediction of crude extract of Atriplex nitens Schkuhr for the screening of antioxidant and urease inhibitory

Atriplex nitens Schkuhr (ANS), which grows naturally in arid and semi-arid regions of the world, is highly resistant to drought and salty environments and is used as food and animal feed. This study first performed phytochemical analysis and antioxidant and urease inhibition activities on the obtained methanol crude extract of ANS. The catechin and isoquercitrin were detected as the main compounds according to LC-MS/MS results. Oleic acid methyl ester (31.71%), palmitic acid methyl ester (25.87%), linoleic acid methyl ester (19.61%), and nonacosane (16.81%) were detected in GC-MS/MS analysis of extract. Posphomolybdenum reducing, DPPH˙ scavenging, and urease inhibition activities were found effective at 67.27±23.83, 7.85±0.44 and 6.58±0.48 µg/mL, respectively, of ANS extract. In this investigation, the biological activity and chemical composition of the ANS extract were initially examined. Molecular docking and ADMET prediction were performed on this plant's two most abundant components. It was found that the interaction with urease of isoquercitrin (MolDock score-121.42, binding affinity -8.60, and binding constant 0.62 µM) with urease determined a higher than. These two components have a negligible potential for toxicity. The Boiled Egg plot indicates a significant GIa for catechin. However, isoquercitrin does not exhibit BBB or GLa permeability. It was determined that the main component isoquercitrine may be effective against gastric diseases, and it was supported that it was not observed in the BBB and GLa systems.

A potential DNA protector, enzyme inhibitor and in silico studies of daucosterol isolated from six Nepeta species

Phytochemical contents and in vitro activities of Berberis thunbergii hydroethanolic extract

Berberis thunbergii, also known as Japanese dogwood, has many medicinal properties due to its rich phytochemical components. Therefore, B. thunbergii hydroethanolic extract was investigated phytochemical content, antioxidant, anti-inflammatory, and enzyme inhibition activities. In LC-MS/MS and GC-MS/MS analysis, the main components of the extract were determined as chlorogenic and oleic acid, respectively. Total phenol and flavonoid amounts were found as 259.40±0.96 mg GAE/g extract and 2.60±0.57 mg QE/g extract, respectively. It was recorded that it could reduce iron as 6.38 mg TE/g extract in the FRAP test and had a radical scavenging effect of 85.26% in the DPPH֗ scavenging test. The anti-inflammatory property of the extract was found to be 60.80±2.22 µg/mL, while DFS was found to be 45.23±0.68. Additionally, in enzyme inhibition, it was observed that it inhibited urease at a low level of 44.19±0.22 µg/mL and xanthine oxidase at a high level of 0.91±0.21 µg/mL. It was recorded that it protected DNA with a 57.55% Form I value. Due to its high antioxidant and XO inhibition effects, B. thunbergii is thought to have potential applications in food, cosmetics, and medicine.

Phytochemical contents and antioxidant activity Paliurus spina-christi Miller leaf and seed extracts: PASS predictions, in silico studies on xanthine oxidase and cytochrome P450 1A1

Paliurus spina-christi Miller (PSC) is a shrub plant with important biological activities. For this reason, the phytochemical and biological activities of the PSC leaf and seed extracts were investigated in our study. This study performs phytochemical analyses (total phenol and flavonoid content, LC-ESI-MS/MS, and GC-MS/MS) and bioactivity assays (antioxidant) for the PSC leaves and seeds. In silico study and PASS prediction of main compounds in LC-ESI-MS/MS and GC-MS/MS analysis were also investigated. The leaf extract showed a high total phenolic and flavonoid content. In addition, the contents of hesperidin (25.548 mg/g extract) were high in the LC-ESI-MS/MS and GC-MS/MS analyses. It was noted that the leaf extract's antioxidant activities were higher than standard. The molecular docking of hesperidin with xanthine oxidase and cytochrome P450 1A1 had high MolDock score (-179.68, -149.156) and binding energy (-11.40 kcal/mol, -9.90 kcal/mol), respectively. This investigation pioneered using PSC leaf extracts as food supplements and medicine.

<i>In vitro</i> bioactivities and <i>in silico</i> enzyme interactions of abietatrien-3 <i>β</i> -ol by bio-guided isolation from <i>Nepeta italica</i> subsp. <i>italica</i>

Abietatrien-3β-ol (ATO) was isolated from the aerial part of the Nepeta italica subsp. italica methanol-chloroform extract and studied antioxidant, enzyme inhibition, and DNA protection activities. The plant extract was fractionated by silica gel column chromatography using four different solvents. After the active chloroform fraction was divided into six subfractions under the guidance of bioactivity, ATO was isolated from the fourth active subfraction. The molecular structure of ATO was determined by the NMR techniques and confirmed with literature data. In the antioxidant test, ATO showed excellent DPPH˙ (IC50-1.18 ± 0.11 µg/mL), ABTS˙+ (IC50-1.82 ± 0.00 µg/mL), metal chelating (IC50-2.90 ± 0.05 µg/mL), superoxide anion scavenging (IC50-11.59 ± 0.27 µg/mL), reducing power (A0.5-21.09 ± 1.42 µg/mL), H2O2 (A0.5-57.81 ± 4.54 µg/mL), and phosphomolybdenum reducing (A0.5-124.23 ± 0.69 µg/mL) activities when compared to standards. The DNA protection potential was also found to be strong in Form I (47.89%) and Form II (4.56%) formations. ATO had high inhibitions in AChE (IC50-1.25 ± 0.04 µg/mL), BChE (IC50-1.26 ± 0.03 µg/mL), lipase (IC50-7.58 ± 0.27 µg/mL), and tyrosinase (IC50-9.60 ± 0.03 µg/mL). In molecular docking studies, ATO had a high binding affinity with α-amylase (−8.80 kcal/mol), tyrosinase (−8.10 kcal/mol), and urease (−8.10 kcal/mol) enzymes. In addition, by detailing the interaction of ATO with key enzymes that give the best interactions through molecular docking studies, with molecular dynamics studies, and by performing ADMET and DFT calculations, it was tried to explain that it could be a suitable drug candidate. In light of these studies, ATO is thought to be an effective enzyme inhibitor and a protective molecule against oxidation with its active antioxidant properties.