Computational Insights into Natural Antischistosomal Metabolites as SmHDAC8 Inhibitors: Molecular Docking, ADMET Profiling, and Molecular Dynamics Simulation.

Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.

Silver Nanoparticles Formulation of Flower Head's Polyphenols of Cynara scolymus L.: A Promising Candidate against Prostate (PC-3) Cancer Cell Line through Apoptosis Activation.

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles of these phenolic fractions were established and tested for their cytotoxicity and apoptotic activity. Results showed that silver nanoparticles of a polyphenolic fraction of flower extract (Nano-TP/Flowers) exhibited potent cytotoxicity against prostate (PC-3) and lung (A549) cancer cell lines with IC50 values of 0.85 µg/mL and 0.94 µg/mL, respectively, compared with doxorubicin as a standard. For apoptosis-induction, Nano-TP/Flowers exhibited apoptosis in PC-3 with a higher ratio than in A549 cells. It induced total prostate apoptotic cell death by 227-fold change while it induced apoptosis in A549 cells by 15.6-fold change. Nano-TP/Flowers upregulated both pro-apoptotic markers and downregulated the antiapoptotic genes using RT-PCR. Hence, this extract may serve as a promising source for anti-prostate cancer candidates.

Antioxidant Property of the Egyptian Propolis Extract Versus Aluminum Silicate Intoxication on a Rat's Lung: Histopathological Studies.

In this study, we evaluated the inflammatory responses induced by aluminum silicate (AS) cytotoxicity in rat lungs. The prophylactic effect of propolis extract was evaluated in 60 adult male albino rats. The rats were divided into six groups: (1) a normal, healthy control group; (2) a normal group fed with 200 mL of propolis extract/Kg; (3) a low-dose positive control group injected with 5 mg/kg of AS; (4) a treated group given propolis and a low dose of AS; (5) a high-dose positive control group injected with 20 mg/kg of AS; and (6) a treated group given propolis with a high-dose of AS. At the end of the two-month experiment, the rats' lungs were removed. For each pair of lungs, one portion was subjected to biochemical analysis and the other underwent hematoxylin and eosin (H&E) staining in order to study its histology. The rats that received AS doses displayed significant disorders in their antioxidant contents as well as in their enzymatic activities and their histopathological structures revealed severe damage to their lung tissues. Upon the rats being treated with propolis, the enzymatic and antioxidant contents improved and partial improvements in the lung structures appeared, including minimized congestion, a reduced hemorrhage of blood vessels and preserved bronchioles, alveolar ducts, and alveoli. The prophylactic effectiveness of propolis extract on the cytotoxicity of AS, owing to the antioxidant properties of propolis, were studied.

γ-Butyrolactones from Aspergillus Species: Structures, Biosynthesis, and Biological Activities.

Recently, numerous metabolites possessing uncommon structures and potent bioactivity have been isolated from strains of fungi collected from diverse environments. The genus Aspergillus is known as a rich source of y-butyrolactones. These are a group of fungal secondary metabolites, consisting of a five- membered lactone bearing two aromatic rings, which shows a great variety of biological activities. This review summarizes the research on the biosynthesis, source, and biological activities of the naturally occurring y-butyrolactones that have been isolated from Aspergillus species published over the last decades. More than 75 compounds are described and 65 references are cited.

New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors.

Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1ß-hydroxy-3ß-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3ß-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3ß-acetoxy-20-taraxasten-22-one (3), 3ß-acetoxy-11α-methoxy-olean-12-ene (4), 3ß-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-ß-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), ß-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3ß,21ß-dihydroxy-11α-methoxy-olean-12-ene (16), 3ß-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3ß-acetoxy-urs-12-ene (21), and ß-sitosterol-3-O-ß-D-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D ((1)H and (13)C), 2D ((1)H-(1)H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.