Antioxidant and anticholinesterase activities of amentoflavone isolated from Ouratea fieldingiana (Gardner) Engl. through in vitro and chemical-quantum studies.

Ouratea fieldingiana, popularly known as batiputá, is a tree species easily found in the coastal part of northeastern Brazil. Its leaves are rich in biflavonoids, its major compound being amentoflavone. Biflavonoids are well studied due to their high antioxidant capacity. Alzheimer's disease (AD) is a disease characterized by the progressive loss of neurons. Currently, the pharmacological treatment of AD has four drugs: donepezil, galantamine, rivastigmine and memantine. Where these drugs, with the exception of memantine, are inhibitors of acetylcholinesterase, thus inhibiting the enzyme that destroys acetylcholine, thus increasing the availability of this neurotransmitter. This article aims to determine in vitro and in silico the antioxidant and anticholinesterase action of amentoflavone isolated from the leaves of Ouratea fieldingiana. The antioxidant capacity of amentoflavone was evaluated using the DPPH* free radical scavenging method, with an IC50 of 5.73 ± 0.08 µg/mL. The antiradical properties of the molecule were also studied in silico through several HAT, SET-PT and SPLET mechanisms via DFT M06-2X/6-311++G(d,p). It was found that in the hydrogen atom transfer mechanism (HAT) the best trend was obtained as an anti-radical mechanism. Amentoflavone has the ability to inhibit acetylcholinesterase when tested in vitro, having an IC50 of 8.68 ± 0.73 µg/mL, corroborating its effect in the in silico test, presenting four strong covalent hydrogen bonds for having a bond length up to 2.5 Å. Thus, amentoflavone is an important target for further testing against Alzheimer's disease. Communicated by Ramaswamy H. Sarma.

Hypoglycemic and hepatoprotective effects in adult zebrafish (Danio rerio) of fisetinidol isolated from Bauhinia pentandra: In vivo and in silico assays.

Diabetes mellitus is a chronic metabolic disorder that has been increasing drastically around the worldwide. It is important to emphasize that although many drugs are commercially available to treat diabetes, many of them have shown a number of adverse effects. Therefore, search for new antidiabetic agents is of great interest, and natural products, especially those obtained from plants sources, may be an alternative to available drugs. This study reports the in vivo and in silico evaluation of the hypoglycemic activity of fisetinidol. The conformational analysis confirmed that the fisetinidol compound possesses two valleys in the potential energy curve, showing a stable conformer on the global minimum of the PES defined by the dihedral angle θ (C6-C7-O-H) at 179.9°, whose energy is equal to zero. In addition, fisetinidol has shown promise in glycemic control and oxidative stress caused by hyperglycemia induced by high sucrose concentration, causing hypoglycemic and hepatoprotective effects in adult zebrafish. ADMET studies showed that fisetinidol has high passive permeability, low clearance and low toxic risk by ingestion, and computational studies demonstrated that fisetinidol complexes in the same region as metformin and α-acarbose, which constitutes a strong indication that fisetinidol has the same inhibitory mechanisms of α-acarbose and metformin.Communicated by Ramaswamy H. Sarma.

Antichagasic evaluation, molecular docking and ADMET properties of the chalcone (2E)-3-(2-fluorophenyl)-1-(2-hydroxy- 3,4,6-trimethoxyphenyl)prop-2-en-1-one against Trypanosoma cruzi.

Characterized as a neglected disease, Chagas disease is an infection that, in the current scenario, affects about 8 million people per year, with a higher incidence in underdeveloped countries, Chagas is responsible for physiological disabilities that result in impacts that are slightly reflected in world socioeconomic stability. Although treatments are based on drugs such as Benznidazole, the pathology lacks a continuous treatment method with low toxicological incidence. The present study estimates the anti-chagasic activity of the synthetic chalcone CPN2F based on the alignment between in vitro tests and structural classification in silico studies, molecular docking and ADMET studies. The in vitro tests showed a reduction in the protozoan metabolism in host cells (LLC-MK2). At the same time, the molecular docking models evaluate this growth inhibition through the synergistic effect associated with Benznida- zole against validated therapeutic target key stages (Cruzaine TcGAPDH and Trypanothione reductase) of the Trypanosoma cruzi development cycle. The in silico prediction results reveal an alignment between pharmacokinetic attributes, such as renal absorption and release, which allow the preparation of CPN2F as an antichagasic drug with a low incidence of organic toxicity.Communicated by Ramaswamy H. Sarma.