Enhancement of the biological activity of hydroxytyrosol through its oxidation by laccase from Trametes versicolor.

The laccase-catalyzed oxidation of hydroxytyrosol (HT) towards the formation of its bioactive oligomer derivatives was investigated. The biocatalytic oligomerization was catalyzed by laccase from Trametes versicolor in aqueous or various water-miscible organic solvents and deep eutectic solvent (DES)-based media. Mass Spectroscopy and Nuclear Magnetic Resonance were used for the characterization of the products. The solvent system used significantly affects the degree of HT oligomerization. The use of 50 % v/v methanol favored the production of the HT dimer, while other organic solvents as well as DESs led to the formation of hydroxytyrosol trimer and other oligomers. In vitro studies showed that the HT dimer exhibits 3- to 4-fold enhanced antibacterial activity against Gram-positive and Gram-negative bacteria compared to the parent compound. Moreover, the ability of HT dimer to inhibit the activity of soybean lipoxygenase and Candida rugosa lipase was 1.5-fold higher than HT, while molecular docking supported these results. Furthermore, HT dimer showed reduced cytotoxicity against HEK293 cells and exhibited a strong ability to inhibit ROS formation. The enhanced bioactivity of HT dimer indicates that this compound could be considered for use in cosmetics, skin-care products, and nutraceuticals.

Supercritical carbon-oxide extracts from cultivated and wild-grown Ganoderma lucidum mushroom: differences in ergosterol and ganoderic acids content, antioxidative and enzyme inhibitory properties.

In the present study, we investigated the effect of supercritical carbon-oxide (scCO2) extraction on antioxidant capacity, enzyme inhibitory potential, and levels of ergosterol and ganoderic acid in both cultivated and wild-grown G. lucidum. Extraction yields were slightly higher for wild samples (1.29%) than for cultivated ones (1.13%). The levels of ganoderic acid and ergosterol were higher in cultivated in comparison to wild samples. In addition, the total phenolic content in cultivated samples (13.42 mg GAE g-1) was higher than in wild samples (10.38 mg GAE g-1). In general, cultivated samples exhibited stronger antioxidant potential when compared with wild ones. Regarding enzyme inhibitory properties, it was validated that the wild samples (14.01 mg OE g-1) possessed greater lipase activity in comparison to cultivated samples (5.36 mg OE g-1). Based on our findings, cultivated G. lucidum might be considered a valuable source of natural bioactive agents in the preparation of health-promoting products.

The Combination of Untargeted Metabolomics with Response Surface Methodology to Optimize the Functional Potential of Common Duckweed (Lemna minor L.).

The present study was designed to evaluate the functional potential of common duckweed (Lemna minor L.) as a source of bioactive compounds of nutraceutical interest. The untargeted profiling of the bioactive components of common duckweed was carried out through ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), in parallel with assessing in vitro antioxidant and enzymatic inhibition properties. The optimization of extraction parameters was determined using the response surface methodology (RSM) through a 3-factor central composite design. The process parameters included extraction temperature, % of ethanol, and ultrasound power, while the response variables were the phenolic content (considering each main phenolic class), total glucosinolates, total carotenoids, the antioxidant potential, and enzyme inhibition activities. The results revealed that common duckweed was a rich source of carotenoids and total flavonoids (mainly flavones and flavonols), followed by phenolic acids, low-molecular-weight phenolics, and glucosinolates. Interestingly, the total flavones, total flavonols and total carotenoid equivalents showed the highest and most positive correlation values with the bioactive properties measured. Finally, the combined RSM approach and unsupervised statistics allowed us to point out the pivotal impact of ethanol percentage in the extraction solvent to recover the highest amounts of bioactive compounds efficiently.

Chemical Profile, Antioxidant and Enzyme Inhibition Activities of Natural Saudi Sidr and Talh Honeys.

Honey is used since ancient time as a food and to cure many diseases. The present study investigated the chemical constituents, antioxidant and enzyme inhibition activities of natural Saudi Sidr (SH) and Talh (TH) honeys. Beside entire honey samples, ethyl acetate, ethanol and water extracts were prepared. The total polyphenolic content of SH, TH and their extracts was in the range of 2.86-7.21 and 3.80-17.33 mg gallic acid equivalents/g, respectively and the total flavonoids content was in the range of 0.05-1.17 and 0.18-2.38 mg rutin equivalents/g, respectively. Out of the 53 standards analyzed by HPLC, 27 compounds were detected with highest number of compounds identified in the ethyl acetate extract of TH (45 %, 24/53) and SH (26 %, 14/53), respectively. Quinic acid was dominant compound identified in all honey samples with the highest content determined in TH ethanol extract (4454 µg/g). The majority of tested samples possessed considerable anti-radicals and reducing ions capacity with the ethyl acetate extract from TH exerted significantly (p<0.05) the highest activity. All honey samples did not show chelating iron metal property. Honey samples revealed variable enzyme inhibition activity with TH (entire and/or ethyl acetate extract) showed significantly (p<0.05) the highest acetylcholinesterase, butyrylcholinesterase, tyrosinase and α-amylase inhibition activity. In conclusion, ethyl acetate is the best solvent for extraction of bioactive molecules from the two honey types. Moreover, the dark-colored TH contained the highest number of molecules and consequently exerted the best antioxidant and enzyme inhibition activities in most assays.

Minerals, phenolics, and biological activity of wild edible mushroom, Morchella steppicola Zerova.

Tasteful morels (Morchella sp.) are one of the most popular mushrooms, both economically and scientifically. Due to their beneficial constituents, they are classified as functional foods. This study focuses on the chemical composition and biological activities of a wild edible mushroom, Morchella steppicola Zerova. The metal composition of this species reveals high levels of biogenic elements. However, according to the levels of iron and cobalt, and calculated health risk indices, this mushroom can be recommended for occasional consumption. Also, M. steppicola is found to be rich in gallic acid, protocatechuic acid, 4-hydroxybenzoic acid, and vanillic acid. Statistical analysis showed that mainly 4-hydroxybenzoic and vanillic acids are responsible for both antioxidant and inhibition of enzymes α-amylase and tyrosinase. Presented work acknowledges the fact that this mushroom has significant potential to be used for the treatment of several human disorders, similarly to other members of this genus.

Phytochemical Profiling, In Vitro Biological Activities, and In Silico Molecular Docking Studies of Dracaena reflexa.

Dracaena reflexa, a traditionally significant medicinal plant, has not been extensively explored before for its phytochemical and biological potential. The present study was conducted to evaluate the bioactive phytochemicals and in vitro biological activities of D. reflexa, and perform in silico molecular docking validation of D. reflexa. The bioactive phytochemicals were assessed by preliminary phytochemical testing, total bioactive contents, and GC-MS analysis. For biological evaluation, the antioxidant (DPPH, ABTS, CUPRAC, and ABTS), antibacterial, thrombolytic, and enzyme inhibition (tyrosinase and cholinesterase enzymes) potential were determined. The highest level of total phenolic contents (92.72 ± 0.79 mg GAE/g extract) was found in the n-butanol fraction while the maximum total flavonoid content (110 ± 0.83 mg QE/g extract) was observed in methanolic extract. The results showed that n-butanol fraction exhibited very significant tyrosinase inhibition activity (73.46 ± 0.80) and acetylcholinesterase inhibition activity (64.06 ± 2.65%) as compared to other fractions and comparable to the standard compounds (kojic acid and galantamine). The methanolic extract was considered to have moderate butyrylcholinesterase inhibition activity (50.97 ± 063) as compared to the standard compound galantamine (53.671 ± 0.97%). The GC-MS analysis of the n-hexane fraction resulted in the tentative identification of 120 bioactive phytochemicals. Furthermore, the major compounds as identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between the ligands and the enzymes (tyrosinase, acetylcholinesterase, and butyrylcholinesterase enzymes). The results of this study suggest that Dracaena reflexa has unquestionable pharmaceutical importance and it should be further explored for the isolation of secondary metabolites that can be employed for the treatment of different diseases.

Synthesis, predictions of drug-likeness, and pharmacokinetic properties of some chiral thioureas as potent enzyme inhibition agents.

A series of chiral thioureas (1 - 17) were synthesized from and tested for their anticholinesterase, tyrosinase, and urease enzyme inhibitor activities. Various phenylisothiocyanates were added to solution of l-cysteine in methanol: water (1 : 1 v/v) at room temperature and stirred for 24 h. The precipitated solid was recrystallized from n-butanol. Pure compounds were characterized by NMR (1H and 13C), FTIR, and CHNS. Tertiary amine containing N-(4-(diethylamino)phenyl)-N'-(2-mercapto-carboxyethanyl)thiourea 17, N-(4-(dimethylamino)phenyl)-N'-(2-mercapto-carboxyethanyl)thiourea 16 and trimethoxy containing N-(3,4,5-trimethoxyphenyl)-N'-(2-mercapto-carboxyethanyl)thiourea 14 were more active than galantamine against AChE and BChE enzymes. In tyrosinase enzyme inhibition activity, compound 14, 10, 12, 6, 13, and 11 exhibited higher tyrosinase inhibitory activity showing IC50 values of 1.1 ± 0.1, 1.5 ± 0.3, 1.6 ± 0.6, 1.9 ± 0.5, 2.2 ± 0.9 and 2.9 ± 0.2 mM, respectively. In urease enzyme inhibition activity assay, 17 showed higher activity. This work demonstrates the pharmacological significance of chiral thiourea derivatives synthesized from l-cysteine and shows their potential. There is a need to perform more in vitro and in vivo biological activities followed by clinical trials to bring such thiourea to the market.

Biological potential of copper complexes: a review.

This review comprises the inorganic compounds particularly metal coordinated complexes, as drugs play a relevant role in medicinal chemistry. It has been observed that copper complexes are potentially attractive as medicinal importance. In this review, the most remarkable achievements of copper complexes undertaken over the past few decades as antimicrobial, antioxidant, enzyme inhibition activity, and anti-cancer agents are discussed. This work was motivated by the observation that no comprehensive surveys of the diversity of biological activities of copper complexes were available in the literature.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential / Síntese verde de nanaopartículas de ouro utilizando extratos de tubérculos Delphinium chitralense, sua caracterização e potencial inibitório enzimático

Greeen synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential

Abstract Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Resumo A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Synthesis of benzoyl hydrazones having 4-hydroxy-3,5-dimethoxy phenyl ring, their biological activities, and molecular modeling studies on enzyme inhibition activities.

Hydrazone compounds have high capacity in terms of antioxidant activity and enzyme inhibition activities such as anticholinesterase, tyrosinase, and urease. In this study, benzoyl hydrazones compounds (7a-7m) were synthesized starting from 3,5-dimethoxy-4-hydroxybenzaldehyde. Antioxidant activity of the synthesized compounds was evaluated. In the ß-carotene-linoleic acid and ABTS cation radical scavenging activities, compounds 7j, 7e, and 7m stood out as the most active compounds, respectively. In the anticholinesterase enzyme inhibition activity results, compound 7f exhibited the best activity against AChE and BChE enzymes in the synthesis series. In addition, molecular docking analysis was performed to understand the inhibition mechanism of the synthesized compounds with target enzymes at the atomic level. In the light of biological activity and in silico studies, it has the potential to guide studies for the development of new drugs for Alzheimer disease in the future.

Phytochemical profiling of Blumea laciniata (Roxb.) DC. and its phytopharmaceutical potential against diabetic, obesity, and Alzheimer's.

Blumea laciniata (Roxb.) DC. is a folk medicinal annual herb of the Asteraceae family that grows in South and Southeast Asia. In order to evaluate its phytopharmaceutical potential against diabetic, obesity, and Alzheimer's, a comprehensive phytochemical profile, in vitro and in silico enzyme inhibitory activity against α-amylase, α-glucosidase, lipase, cholinesterases, and tyrosinase along with in vitro antioxidant activity were performed. Additionally, in vivo antidiabetic activity and acute toxicity were also evaluated. The total phenolic content in various organs follows the following order: old leaf > flower bud > young leaf > flower > young stem > old stem > root, while total flavonoids followed the order: flower bud > old leaf > young leaf > flower > young stem > old stem > root. The identified phenolic compounds are 3,4-dihydroxybenzoic acid, caffeic acid, vanillic acid, p-coumaric acid, syringic acid, rosmarinic acid, trans-cinnamic acid, catechin, catechol, (-) epicatechin, rutin, quercetin, myricetin, and kaempferol, which are also expressed differently in various organs. Solvent extracts demonstrated strong antioxidant activity as well as varying levels of inhibition against the enzymes tested, with strong inhibitory activity against α-amylase, α-glucosidase, and lipase. Thirteen phenolic compounds displayed strong binding affinity in silico against studied enzymes, thus documented as bioactive. Furthermore, solvent extracts significantly suppressed blood glucose levels in mice with induced diabetes and extracts were not acutely toxic. The results suggest that Blumea laciniata (Roxb.) DC. could be a potential candidate for developing new phytopharmaceuticals and bioactive ingredients.

Supercritical and ultrasound-assisted extracts from Pleurotus pulmonarius mushroom: chemical profiles, antioxidative, and enzyme-inhibitory properties.

BACKGROUND: This study provides an insight into the impact of ultrasound-assisted extraction with water as solvent (UAEW) and extraction by supercritical carbon dioxide (SC-CO2 ) with 5% EtOH on antioxidant and enzyme inhibitory activity in regard to the chemical profile of the edible and medicinal mushroom, Pleurotus pulmonarius. RESULTS: Extraction efficiency was between 0.36% and 63.32%, depending on the extraction technique. The main compounds in the extracts were fatty acids. Supercritical CO2 extraction with co-solvent was the most suitable method for obtaining extracts that were rich in ergosterol content, reaching a value of 40.1 mg g-1 . The UAEW of crude mushroom powder ensured the highest yield, as well as the extracts with best antioxidative activity. The measurements of enzyme inhibitory activity revealed that all types of investigated extracts exhibited only tyrosinase and amylase inhibition at a significant level. CONCLUSION: Based on our results, the extraction methods significantly affected the chemical profile and bioactivity of P. pulmonarius. © 2020 Society of Chemical Industry.

Phytocomplex Characterization and Biological Evaluation of Powdered Fruits and Leaves from Elaeagnus angustifolia.

Fully ripe fruits and mature leaves of Elaeagnus angustifolia were harvested and analyzed by means of analytical and biological tests to better comprehend the chemical composition and therapeutic/nutraceutical potential of this plant. Fruits and leaves were dried and the obtained powders were analyzed to study their color character and (via headspace gas chromatography) describe the chemical profile. Subsequently, they were submitted to a chloroform-methanol extraction, to a hydroalcoholic extraction procedure assisted or not by microwaves, and to an extraction with supercritical CO2, assisted or not by ethanol as the co-solvent, to detect the polyphenolic and the volatile content. The resulting extracts were evaluated in terms of chlorophyll and carotenoid content, polyphenolic content, volatile fraction, total phenolic content, total flavonoid content, antioxidant activity, radical scavenging activity, and enzymatic inhibition activity. The results confirmed the correlation between the chemical composition and the high antioxidant potential of leaf extracts compared to the fruit extracts in terms of the phenolic and pigment content. A promising effect against tyrosinase emerged for all the extracts, suggesting a therapeutic/nutraceutical use for this plant. Conversely, the volatile content from both natural matrices was similar.

Semi-Continuous Subcritical Water Extraction of Flavonoids from Citrus unshiu Peel: Their Antioxidant and Enzyme Inhibitory Activities.

We extracted and hydrolyzed bioactive flavonoids from C. unshiu peel using subcritical water (SW) in a semi-continuous mode. The individual flavonoid yields, antioxidant and enzyme inhibitory activities of the SW extracts were analyzed. The extraction yields of hesperidin and narirutin increased with increasing temperature from 145 °C to 165 °C. Hydrothermal hydrolysis products (HHP), such as monoglucosides (hesperetin-7-O-glucoside and prunin) and aglycones (hesperetin and naringenin) were obtained in the SW extracts at temperatures above 160 °C. The sum of hesperidin and its HHP in the SW extracts was strongly correlated with antioxidant activities, whereas the contents of hesperetin and naringenin were strongly correlated with enzyme inhibitory activities. Hesperetin exhibited the highest antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, ferric-reducing antioxidant power, and oxygen radical absorbance capacity), whereas hesperetin-7-O-glucoside exhibited the highest enzyme inhibitory activities (angiotensin-І converting enzyme (ACE) and pancreatic lipase (PL)). Naringenin exhibited the highest enzyme inhibitory activities (xanthine oxidase and α-glucosidase). PMFs (sinensetin, nobiletin, and tangeretin) also exhibited relatively high inhibitory activities against ACE and PL. This study confirms the potential of SW for extracting and hydrolyzing bioactive flavonoids from C. unshiu peel using an environmentally friendly solvent (water) and a shorter extraction time.

First report of a lactonic disecosteroid from the buccinid gastropod Babylonia spirata.

A lactonic steroid with an unprecedented 1, 10: 8, 9-disecoergostane framework was identified from the ethyl acetate-methanol extract of buccinid gastropod mollusk, Babylonia spirata collected from the southwestern coast of Indian peninsular region. The compound was characterized as 1, 10: 8, 9-disecoergosta-8-en-A-homo-6a-oxa-1-one by exhaustive spectroscopic methods including two-dimensional nuclear magnetic resonance and mass spectroscopic investigations. The disecosteroid displayed moderate carbolytic enzyme inhibition activity as distinguished by its inhibitive effects against α-amylase and α-glucosidase (IC50 0.40 and 0.54 mg/mL, respectively). The anti-inflammatory (5-lipoxidase inhibitory) activity of the titled secondary metabolite was found to be superior (IC50 < 0.85 mg/mL) than the commercial anti-inflammatory drug (ibuprofen IC50 > 0.85 mg/mL). However, significantly greater antioxidant property was recorded for the studied disecosteroid as evaluated by in vitro 2, 2-diphenyl-1-picrylhydrazyl radical inhibition potential (IC50 0.30 mg/mL) than that of standard, α-tocopherol (IC50 > 0.50 mg/mL). The in silico molecular docking studies were conducted to explain the anti-5-lipoxidase and anti-α-amylase properties of the isolated compound. The molecular binding interactions of the ligands with the pro-inflammatory 5-lipoxidase and the carbolytic enzyme α-amylase, demonstrated that their binding energies/docking scores were positively associated with their in vitro bioactivities. A plausible pathway for the biosynthetic origin of lactonic disecosteroid in B. spirata was proposed from an ergosterol precursor. Structure-activity correlation study demonstrated that the biological activities of the disecosteroid were directly proportional to their electronic properties allied with lesser steric restrictions.

Fatty Acid and Phytosterol Composition, and Biological Activities of Lycium ruthenicum Murr. Seed Oil.

Lycium ruthenicum Murr. (LRM, Solanaceae), also called "black wolfberry" in China, is extremely tolerant drought. Although black wolfberry has seeds that are rich in oil, being considered as a potential alternative for edible oil production, little information has been found regarding its characterization. The present study evaluated the fatty acid profile of the seed oil and its phytosterol contents. Moreover, its antioxidant potential and its inhibition activities on pancreatic lipase, and cholesterol esterase (CEase) were also determined. The key fatty acids of studied oil were linoleic (74.58%), oleic (11.82%), γ-linolenic (6.60%), palmitic (4.88%), and stearic (1.40%) acids, which together comprised 99.28% of the total fatty acids. Phytosterols including 24-methylenecholesterol, campesterol, stigmasterol, dihydrolanosterol, 24-methyldesmosterol, ß-sitosterol, Δ5 -avenasterol, cycloartenol, and Δ7- avenasterol were identified for the 1st time. The inhibition values (IC50 ) for the DPPH and ABTS radical scavenging capacities of the oil were 7.86 and 15.49 mg/mL, respectively. Additionally, LRM seed oil was also demonstrated to possess strong pancreatic lipase, and CEase inhibition activities with IC50 values of 12.38 and 2.63 mg/mL, respectively. The mechanism study indicated that the inhibitory manner of the oil on CEase belonged to uncompetitive inhibition of reversible inhibition. The results derived from above studies suggest that LRM seed oil could be a potential source of high value phytochemicals for developing novel functional food.

Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors.

Three new norditerpenoids alkaloids, 1ß-hydroxy,14ß-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.

One new indolocarbazole alkaloid from the Streptomyces sp. A22.

One new indolocarbazole alkaloid, 12-N-methyl-k252c, together with eight known indolocarbazoles were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. A22. Their structures were elucidated on the basis of spectroscopic methods (UV, IR, HRESITOF MS, 1D NMR and 2D NMR). All of these compounds were evaluated for bromodomain-containing protein 4 (BRD4) inhibitory activities and cytotoxic activity assay, respectively. Compounds 4 and 5 showed moderate cytotoxic activity with an IC50 value of 3.52 and 3.93 µM, respectively. Additionally, compound 1 also was tested for enzyme inhibition activities of protein kinases and showed moderate activity with IC50 values of 0.91-1.84 µM.

Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum.

Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6ß-Methoxy, 9ß-dihydroxylheteratisine (1), 1α,11,13ß-trihydroxylhetisine (2), 6,15ß-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.