Band 77, Heft 11-12

In this study, two novel series of thiazolylhydrazone derivatives containing 4-ethylpiperazine ( 3a–3f ) and 4-methoxyphenylpiperazine ( 3g – 3l ) side chains were synthesized and their structures were characterized by spectral ( 1 H NMR, 13 C NMR, and MS spectra) analyses. In vitro inhibitory activities of synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined by Ellman method. According to the results, all compounds showed a weak inhibitory effect on AChE, while promising results were obtained on BChE. Among the synthesized compounds, the activities of the derivatives carrying 4-ethylpiperazine ( 3a–3f ) structure were found to be more effective than the compounds carrying 4-methoxyphenyl piperazine ( 3g – 3l ) derivatives. Especially, compound 3f bearing the nitro substituent was found to be the most promising compound on BChE in the series. The absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were predicted by using the SwissADME server. The potential binding mode and stability of compound 3f with BChE were investigated by the molecular docking and dynamics simulations. The results showed that 3f was strongly bound up with BChE with the optimal conformation; in addition, their binding free energy reached −167.936 ± 13.109 kJ/mol.

Snakebite envenoming is a health concern and has been a neglected tropical disease since 2017, according to the World Health Organization. In this study, we evaluated the ability of ten 1,2,3-triazole derivatives AM001 to AM010 to inhibit pertinent in vitro (coagulant, hemolytic, and proteolytic) and in vivo (hemorrhagic, edematogenic, and lethal) activities of Bothrops jararaca venom. The derivatives were synthesized, and had their molecular structures fully characterized by CHN element analysis, Fourier-transform infrared spectroscopy and Nuclear magnetic resonance. The derivatives were incubated with the  B. jararaca venom (incubation protocol) or administered before (prevention protocol) or after (treatment protocol) the injection of B. jararaca venom into the animals. Briefly, the derivatives were able to inhibit the main toxic effects triggered by B. jararaca venom, though with varying efficacies, and they were devoid of toxicity through in vivo , in silico or in vitro analyses. However, it seemed that the derivatives AM006 or AM010 inhibited more efficiently hemorrhage or lethality, respectively. The derivatives were nontoxic. Therefore, the 1,2,3-triazole derivatives may be useful as an adjuvant to more efficiently treat the local toxic effects caused by B. jararaca envenoming.

The coronavirus (SARS-CoV-2) pandemic is rapidly advancing and spreading worldwide, which poses an urgent need to develop anti-SARS-CoV-2 agents. A human receptor, namely, angiotensin-converting enzyme 2 (ACE-2), supports the SARS-CoV-2 entry, therefore, serves as a target for intervention via drug. In the current study, bioinformatic approaches were employed to screen potent bioactive compounds that might be ACE-2 receptor inhibitors. The employment of a docking study using ACE receptor protein with a ready-to-dock database of phytochemicals via MOE software revealed five compounds as potent molecules. Among them, astragaloside exhibited the highest binding affinity −21.8 kcal/mol and stable interactions within the active site of the ACE-2 receptor. Similarly, the phytochemicals such as pterocaryanin B, isoastragaloside II, and astraisoflavan glucoside followed by oleuropein showed a stronger binding affinity. We hypothesize these compounds as potential lead candidates for the development of anti- COVID-19 target-specific drugs.

The sole difference between white tea (WT) and green tea (GT) is the former that made only from the buds and young leaves of the Camelia sinensis plant, whilst the latter is made from matured tea leaves. The phytochemical profiles, phenolic compounds, antioxidant, and antimicrobial activity of two varieties of Camellia sinensis teas, white and green, were compared in this study. Total antioxidant capacity, reducing power, DPPH radical scavenging, and Fe +2 chelating activities were used to determine antioxidant activities in water extract of GT and WT. The largest level of phenolic content was discovered in WGTE compared with the lowest amount was found in WWTE (290.67 mg/100 g tea and 185.96 mg/100 g tea, respectively). Phenoilc acids (gallic, benzoic, chlorogenic, ellagic, and ρ-coumaric acids) and flavonoids (rutin and kampherol) were found in the two extracts. The findings of DPPH radical scavenging assays were 84.06 and 82.37% inhibition. In vitro antimicrobial activity was indicated that (WWTE and WGTE) had a high level of activity against Staphylococcus aureus, and gave negative activity against Salmonella typhimurium, and Aspergillus Niger . The WT and GT extracts are a great source of natural antioxidants with biological effects on human health.

Diabetes is characterized by hyperglycemia and a significant risk of vascular complications. Vascular endothelial growth factor (VEGF) and its main receptor VEGFR2 (KDR), which is highly expressed in vascular endothelial cells, are essential mediators of vascular maintenance and angiogenesis. During glycolysis after high calorie food intake, methylglyoxal (MGO) is formed and MGO blood levels are elevated in diabetes. MGO reacts with arginine residues to generate MG-H1 or with lysine residues to carboxyethyl lysine which are common components of advanced glycation end-products. Therefore, the question arises whether hyperglycemic conditions affect VEGF signaling via a ligand-independent direct modification of signaling components. As a first step, the effect of MGO on VEGFR2 activation was investigated in cultured endothelial cells from human umbilical vein by determination of VEGFR2 phosphorylation at selected tyrosine residues by ELISA and immunoblotting using phospho-specific antibodies. Phosphorylation of VEGFR2-Y996, VEGFR2-Y1054, or VEGFR2-Y1175 reached a maximum 5 min after stimulation of endothelial cells with VEGF. Phosphorylation was significantly inhibited by 100 µM MGO and to a lesser extent by high glucose treatment. 2,3-Pentanedione and glyoxal were investigated for comparison. In summary, VEGFR2 phosphorylation is sensitive to MGO or high glucose concentrations which may be relevant in the pathophysiology of microvascular disease in diabetes.

Two new alkaloids ( 1 and 2 ), named 1,7-dimethoxy-2′-prenyl-1′,9-dihydropyrrolo-carbazole ( 1 ) and 1,7-dimethoxy-4′,5′-dimethylcyclopenta-carbazole-1′,3′-dione ( 2 ), along with thirteen known alkaloids ( 3 – 15 ) were isolated by means of silica gel, sephadex LH-20, and semi-preparative HPLC from the CHCl 3 extraction of Corydalis decumbens for the first time. Their structures were determined by NMR, MS, IR, UV, and related references. Compounds ( 1 – 15 ) were evaluated for their antidepressant activities by measuring inhibition of monoamine neurotransmitter reuptake in vitro . Among them, compounds 1 , 2 , 4 , and 6 showed certain antidepressant activities.

In this study, novel pyridine-containing thiazolyl hydrazone derivatives were synthesized. Structure determinations of the compounds were performed using 1 H NMR, 13 C NMR and HRMS techniques. The biological activities of the compounds were evaluated against MAO enzymes by in vitro fluorometric method. As a result of activity studies, compound 3a showed selective inhibitory activity against MAO-B enzyme with IC 50  = 0.088 + 0.003 µM. The selectivity index of this compound is greater than 1136. Molecular docking studies were carried out using 2V5Z crystal. It has been observed that docking studies and activity studies are in harmony.

Several Magnolia species have exhibited potent biological activities such as anti-inflammatory, anti-angiogenesis, anticonvulsant, anti-obesity, and antiviral activities. However, the Magnolia candollii from Malaysia has not been investigated yet. Hence, this study aims to investigate the chemical composition and bioactivities of the essential oil of Magnolia candollii H.Keng from Malaysia. The hydrodistillation process was used to produce the essential oil, and gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were used to analyse it. In total, 44 chemical components were identified in the bark oil, accounting for 98.4%. The major components of the essential oil were α-pinene (29.7%), elemol (10.2%), β-pinene (8.5%), β-caryophyllene (7.2%), α-terpineol (7.0%), guaiol (5.4%), and bulnesol (4.9%). Acetylcholinesterase and anti-inflammatory activities were also evaluated using the Ellman method and lipoxygenase enzyme, respectively, in which the essential oil showed moderate inhibitory activity against acetylcholinesterase (I%: 70.2%) and lipoxygenase (I%: 72.5%). Thus, the findings may be helpful for identifying the medicinal and therapeutic uses of the essential oil from the Magnolia genus.

Essential oils obtained from medicinal plants show high therapeutic potential against several types of pathologies, including Alzheimer’s disease. The purpose of this work was to study the chemical composition and anticholinesterase inhibitory activity of the essential oil obtained from Lepisanthes rubiginosa leaves collected from Malaysia. Twenty-four components were identified using gas chromatography-flame ionization detection (GC-FID) and gas chromatography/mass spectrometry (GC-MS), which represent 99.5% of the essential oil. The identified major components include α-cadinol (40.0%), safrole (12.6%), α-amorphene (9.5%), ( E )-isosafrole (5.0%), δ-cadinene (4.2%), and t-muurolol (4.1%). Anticholinesterase activity was assessed using Ellman method, and the essential oil demonstrated a moderate inhibitory activity against acetylcholinesterase (I%: 75.2%) and butyrylcholinesterase (I%: 70.2%) at conconcetration of 1000 μg/mL. The current study is the first to report chemical composition and anticholinesterase activity of the essential oil obtained from L. rubiginosa , which may have implications on the characterization, pharmaceutical, and therapeutic applications of Lepisanthes genus essential oils.