In vitro acetylcholinesterase and butyrylcholinesterase inhibitory potentials of essential oil of Artemisia macrocephala

In this study we screened the essential oil of Artemisia macrocephala for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials. Ellman's assay method was used to investigate the enzyme inhibitory potential of the essential oil. The oil sample showed 87.7 ± 1.2, 77.9 ± 0.6, 74.5 ± 1.9 and 62.5 ± 0.3 percent AChE inhibition at 1000, 500, 250 and 125 ?g/mL concentrations respectively with IC50 value of 40 ?g/mL. Similarly it showed 81.8 ± 0.6, 75.6 ± 1.2, 70.0 ± 0.6 and 64.2 ± 1.4 percent BChE inhibition in 1000, 500, 250 and 125 ?g/mL concentrations respectively with IC50 value of 30 ?g/mL. The results of this study confirm the beneficial applications of the oil sample in the treatment of various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, ataxia and all other forms of dementia

Interplay of weak noncovalent interactions in alkoxybenzylidene derivatives of benzohydrazide and acetohydrazide: a combined experimental and theoretical investigation and lipoxygenase inhibition (LOX) studies

In this study, three new hydrazide-based Schiff bases (1-3) have been synthesizedviasonication in good to excellent yields 73-90% and mainly characterized by UV-visible, IR,1H-NMR and single crystal X-ray diffraction analysis. The crystal structure of compounds1and2is stabilized by N-H⋯O, C-H⋯O and C-H⋯N hydrogen bonds, as well as C-H⋯π contacts. In addition, weak π⋯π stacking interactions were observed in the structure of2. A detailed analysis of the intermolecular interactions that stabilize the crystal packing has been performed by using Hirshfeld surface analysis and energy framework calculations were carried out to analyze and visualize the topology of the supramolecular assembly, indicating that the dispersion energy is dominant over the electrostatic one in the most energetic dimers of both compounds. The interaction energies associated with the noncovalent interactions observed in the crystal structures and the interplay between them have been calculated using DFT calculations. Moreover, these intermolecular interactions were also characterized by using both Bader´s quantum theory of atoms in molecules (QTAIM) and NCI plots. The synthesized alkoxybenzylidene analogs of benzohydrazide and acetohydrazide were screenedin vitroagainst soybean lipoxygenase and were found to show better activity than the standard indomethacin. Putative binding modes and comparison of binding interactions in the protein-ligand complex were analyzed by molecular docking studies.Fil: Ahmed, Muhammad Naeem. University of Azad Jammu and Kashmir; PakistánFil: Arif, Muneeba. University of Azad Jammu and Kashmir; PakistánFil: Andleeb, Hina. Quaid-i-Azam University; Pakistán. International Islamic University Islamabad; PakistánFil: Ali Shah, Syed Wadood. University of Malakand; PakistánFil: Arshad, Ifzan. Quaid-i-Azam University; PakistánFil: Tahir, Muhammad Nawaz. University of Sargodha; PakistánFil: Rocha, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; ArgentinaFil: Gil, Diego Mauricio. Universidad Nacional de Tucumán. Instituto de Biotecnología Farmacéutica y Alimentaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Biotecnología Farmacéutica y Alimentaria; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; Argentin

Synthesis of new isoquinoline-base-oxadiazole derivatives as potent inhibitors of thymidine phosphorylase and molecular docking study

Here in this study regarding the over expression of TP, which causes some physical, mental and socio problems like psoriasis, chronic inflammatory disease, tumor angiogenesis and rheumatoid arthritis etc. By this consideration, the inhibition of this enzyme is vital to secure life from serious threats. In connection with this, we have synthesized twenty derivatives of isoquinoline bearing oxadiazole (1–20), characterized through different spectroscopic techniques such as HREI-MS, 1H- NMR and 13C-NMR and evaluated for thymidine phosphorylase inhibition. All analogues showed outstanding inhibitory potential ranging in between 1.10 ± 0.05 to 54.60 ± 1.50 µM. 7-Deazaxanthine (IC50 = 38.68 ± 1.12 µM) was used as a positive control. Through limited structure activity relationships study, it has been observed that the difference in inhibitory activities of screened analogs are mainly affected by different substitutions on phenyl ring. The effective binding interactions of the most active analogs were confirmed through docking study

Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

<p>Abstract</p> <p>Background</p> <p><it>Callistemon citrinus </it>Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of <it>Callistemon citrinus </it>were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it.</p> <p>Methods</p> <p>The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with <it>n-</it>hexane, chloroform, ethyl acetate and <it>n-</it>butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift.</p> <p>Results</p> <p>Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD₅₀value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC₅₀value for brine shrimp cytotoxicity is 65.5 ± 7.28 (60.8- 69.4, n = 4) mg/ml. All the fractions relaxed the spontaneous and KCl-induced contractions. EC₅₀values (mg/ml) for effects of ethyl acetate fraction on spontaneous and KCl induced contractions are 2.62 ± 0.78 (2.15-3.0, n = 4) and 3.72 ± 0.86 (3.38-4.28, n = 4) respectively. Respective EC₅₀values (mg/ml) for <it>n-</it>butanol fraction are 3.59 ± 0.2(3.07-3.9, n = 4) for spontaneous, and 5.57 ± 0.2 (5.07-6.11, n = 4) for KCl- induced contractions. EC₅₀value for control calcium chloride curve (without extract) is -2.73 ± 0.19 (-2.6 - -2.81, n = 4) while EC₅₀for curves treated with 5.0 mg/ml of chloroform is -2.22 ± 0.02 (-2.16 - -2.3, n = 4). EC₅₀value for ethyl acetate treated (1.0 mg/ml) tissues is -1.95 ± 0.10 (-1.88 - -2.0, n = 4) <it>vs</it>. control EC₅₀= -2.71 ± 0.08 (-2.66 - -2.76, n = 4). All the fractions, except <it>n-</it>hexane, showed a right shift like that of verapamil (EC₅₀= -1.72 ± 0.15 (-1.62 - -1.8, n = 4) vs. Control EC₅₀= -2.41 ± 0.06 (-2.38 - - 2.44, n = 4), a standard drug that blocks voltage operated calcium channels.</p> <p>Conclusion</p> <p>Relaxant constituents were more concentrated in ethylacetate fraction followed by chloroform, <it>n -</it>butanol and aqueous fractions that warrant for its isolation. The crude methanol extract is safe at concentration 250 mg/ml or below and results of brine shrimp cytotoxicity assay imply the plant specie may be a source of cytotoxic agents.</p

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden