Phytochemical, antioxidant and anticholinesterase profiles of Musanga cecropioïdes R. Br. (Urticaceae) from Côte d'Ivoire

This study is devoted to Musanga cecropioides (Urticaceae), a tropical plant whose leaves and root bark are used in traditional medicine in the treatment of various pathologies. The objective of this work was to study qualitative and quantitative composition of phenolic compounds in extracts of the leaves (McF) and root bark (McR) Musanga cecropioides and to evaluate their antioxidant and anticholinesterase properties. Phytochemical screening using TLC showed that the extracts contain, along with phenolic compounds such as coumarins, flavonoids and tannins, other bioactive phytocompounds namely sterols, terpenes and alkaloids. Quantitative analysis of phenolic phytoconstituents by spectrophotometry showed that contents of total flavonoids and polyphenols in leaves (7.753% and 119.389 mg EAG / g, respectively) are higher than those in the root bark (1.41% and 105.944 mg EAG / g, respectively). The antioxidant activity of total and selective extracts evaluated by FRAP and DPPH methods was found to be significant compared to vitamin C. All the extracts of Musanga cecropioides showed good anticholinesterase activity with percentages of inhibition of the acetylcholinesterase (AChE) ranging from 51.952 to 63.589%.

Study of the Alkaloid Polyneuridine as a Drug Candidate for Therapy of Alzheimer's Disease

Alzheimer's disease is characterized by the progressive and irreversible loss of natural cognitive functions in most elderly people. There is currently no cure for this neurodegenerative disorder, but there are therapies available on the market based on substances that inhibit acetylcholinesterase and cognitive symptoms as a way to improve cholinergic hypofunction. Polyneuridine is the main indole alkaloid extracted from the bark and leaves of Aspidosperma polyneuron, a brazilian plant species popularly known as peroba-rosa. The objective of this work is to investigate, through a scientific prospection, the polyneuridine alkaloid, as well as its anticholinesterase property, since it is known that the therapy of this disease is based on cholinesterase inhibitors. To carry out the study, two of the main publication databases of journals such as PubMed and Web of Science were analyzed. To search for scientific production, we inserted the following keywords combined with the terms in english to carry out the search in international databases: “Polyneuridine”, “Polyneuridine AND anticholinesterase properties”, “Polyneuridine AND Alzheimer's disease”. The need for studies on this alkaloid is urgent, especially since Brazil holds the plant species that produces the most polyneuridine, but the plant species Aspidosperma polyneuron is on the red line of extinction due to the unbridled exploitation of its wood. It is concluded that if this exploration scenario continues, Brazil will lose a very important pharmacological genetic resource of its plant flora.

Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth.

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer’s disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds—(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)—as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1–4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.

Antidiabetic and Anticholinesterase Properties of Extracts and Pure Metabolites of Fruit Stems of Pistachio (Pistacia vera L.)

: Five metabolites were isolated by chromatographic methods from the fruit stems of P. vera and their chemical structures were characterized as masticadienonic acid (1), tirucallol (2), masticadienolic acid (3), pistachionic acid (4) and inulobiose (5) via FT-IR, 1H-NMR, 13C-NMR, 1D-NMR and 2D-NMR. Pistachionic acid (4), a new shikimic acid derivative, was isolated from the ethanol extract for the first time. The hexane, chloroform, ethanol extracts and pure metabolites exhibited antidiabetic properties by inhibiting α- glycosidase and α-amylase enzymes at different rates. Their inhibitory effects against the α- glycosidase enzyme were also higher than that of the acarbose (IC50=10.30 mg/mL). Masticadienolic acid (3) (IC50=0.03 mg/mL), masticadienonic acid (1) (IC50=0.13 mg/mL) and hexane extract (IC50=0.09 mg/mL) with the lowest IC50 values were found to be most active substances. Nevertheless, the inhibitory effect of acarbose against the α-amylase enzyme was determined to be higher than the inhibition effects of the extracts and pure metabolites. According to the IC50 values, the best inhibitors against the α-amylase were ethanol extract (IC50=5.17 mg/mL), pistachionic acid (4) (IC50=7.35 mg/mL), tirucallol (2) (IC50=7.58 mg/mL) and masticadienolic acid (3) (IC50=8.22 mg/mL), respectively among the applications. In addition, anticholinesterase properties of the extracts and pure metabolites were investigated by testing the inhibitory properties against acetylcholine esterase (AChE) and butrylcholine esterase (BChE) enzymes activities. The results showed that the anticholinesterase properties of all extracts and pure metabolites were weaker than those of the commercial cholinesterase inhibitors, neostigmine and galantamine, and all applications reduced the activity of these enzymes at very high concentrations.

Synthesis and characterisation of novel 4,6-dimethoxyindole-7- and -2-thiosemicarbazone derivatives: Biological evaluation as antioxidant and anticholinesterase candidates

Two sets of novel indole-based thiosemicarbazone systems 8a–d and 9a–d are prepared by the Schiff base condensation reaction of indole carbaldehydes 4 and 6 with a range of thiosemicarbazides 7a–d in high yields and purity. The antioxidant properties of the synthesised compounds 8a–d and 9a–d are determined by employing three different assays, namely 2,2-diphenyl-1-picrylhydrazyl hydrate–free radical scavenging, ABTS [2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] cationic radical decolarization and cupric ion reducing antioxidant capacity. The anticholinesterase properties of the products are investigated by acetylcholinesterase and butyrylcholinesterase enzyme inhibition assays. The methyl-substituted compounds 8b and 9b display the highest inhibition for the ABTS assay and absorbance values for the cupric ion reducing antioxidant capacity assay, while compound 9c shows the best activity for 2,2-diphenyl-1-picrylhydrazyl hydrate assay. Moderate inhibition of acetylcholinesterase and butyrylcholinesterase is determined in the case of compound 8b.