Abstract

Some novel inhibitors based on the (benzo[d]thiazol-2-yl)-1-phenylmethanimine derivatives were designed to reduce the aggregation process in Alzheimer's disease. These structures seem to mimic stilbene-like scaffold, while the benzothiazole moiety “locks” the thioflavin T binding site. Other inhibitors were designed based on 2-((benzo[d]thiazol-2-ylimino)methyl)-5-(benzyloxy)-1-methylpyridin-4(H)-one derivatives.

Benzo[d]thiazol-2-amine derivatives were prepared by the reaction of aniline derivatives with ammonium thiocyanate in the presence of bromine/acetic acid. Then, the reaction of amines with benzaldehyde derivatives and 5-(benzyloxy)-1-methyl-4-oxo-1,4-dihydropyridine-2-carbaldehyde gave the desired compounds. The plate reader-based fibrillation assay was done to evaluate the inhibition of Aβ aggregation. Also, molecular dynamic simulation was carried out to clarify the interaction manner of the designed compounds with Aβ formation.

The biological evaluation proved 5a and 7e as the best inhibitor of the Aβ aggregation. compound 5a in the concentration of 50 μM inhibited Aβ fibril formation better than 7e. MD simulation elucidated that the Aβ aggregation inhibitors in different concentrations represented different binding conformations throughout the entire or in one area of Aβ. MD showed the ligands in lower concentrations accumulate in an area of Aβ aggregations and separate one fibril from the aggregated Aβ. On the contrary, in higher concentrations, the ligands tend to be located through the entire Aβ.

A novel Schiff base namely 3,5-di-tert-butyl-6-((2-(perfluorophenyl) hydrazono) methyl) phenol was successfully synthesized and characterized using FTIR and 1H-NMR, 13C-NMR, and 19F-NMR. The crystal structure analysis of the Schiff base compound was also characterized with single crystal X-ray diffraction studies and supported the spectroscopic results. The cytotoxicity, anti-bacterial properties, and enzyme inhibition of the compound were also investigated. The molecular docking studies were performed in order to explain the interactions of the synthesized compound with target enzymes. The newly synthesized hydrazone derivative Schiff base compound showed high cellular toxicity on MCF-7 and PC-3 cells. Also, this compound caused low antibacterial effect on E. coli and S. aureus. Besides, the compound exhibited the inhibitory effect against pancreatic cholesterol esterase and carbonic anhydrase isoenzyme I, II with IC50 values 63, 99, and 188 µM, respectively. Consequently, it has been determined that the prepared Schiff base is an active compound in terms of cytotoxicity, enzyme inhibition, and anti-bacterial properties. These results provide preliminary information for some biological features of the compound and can play a major role in drug applications of the Schiff base compound.

The novel benzothiazole sulfonate hybrid derivatives containing azomethine group were synthesized and characterized using 1H NMR, 13C NMR, and HRMS analysis. The potential enzyme inhibition activities against pancreatic lipase of the novel benzothiazole sulfonate hybrid derivatives containing azomethine group were screened with in vitro and in silico methods. IC50 values of compounds 5b (23.89 µM), 5i (28.87 µM), and 5f (30.13±4.32) were found to be more effective pancreatic lipase inhibitors than orlistat (57.75 µM) in vitro studies. Also, the binding affinities of compounds 5b (-8.7 kcal/mol), 5i (-8.6 kcal/mol), and 5f (-8.9 kcal/mol) were found potential inhibitors for pancreatic lipase in silico studies. In addition, the absorption distribution, metabolism, and excretion properties (ADME), molecular properties, toxicity estimation, and bioactivity scores of the synthesized compounds were scanned. It was found to have the ability to cross the brain-blood barrier for compounds 5a, 5b, 5c, and 5d. All compounds were calculated to be taken orally as drugs, suitable for absorption in the intestinal tract and not carcinogenic, as well as very strongly bound to plasma proteins. Finally, compound 5f was observed to be the best inhibitor for pancreatic lipase according to in vitro and in silico studies.

Front Cover. This review comprehensively assesses bioactive compounds in Persea species (1950-2023). Different metabolites, such as flavonoids (32), terpenoids (31), fatty alcohols (30), lignoids (19), and γ-lactone derivatives (18) were identified. These compounds displayed diverse properties such as insecticidal, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, and antioxidant. This review enriches the knowledge of bioactive compounds in the genus Persea as reported by main authors et al. in their article at 10.1002/cbdv.202300947.

Abstract

Casearia species are found in the America, Africa, Asia, and Australia and present pharmacological activities, besides their traditional uses. Here, we reviewed the chemical composition, content, pharmacological activities, and toxicity of the essential oils (EOs) from Casearia species. The EO physical parameters and leaf botanical characteristics were also described. The bioactivities of the EOs from the leaves and their components include cytotoxicity, anti-inflammatory, antiulcer, antimicrobial, antidiabetic, antioxidant, antifungal, and antiviral activities. The main components associated with these activities are the α-zingiberene, (E)-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, α-humulene, β-acoradiene, and δ-cadinene. Data on the toxicity of these EOs are scarce in the literature. Casearia sylvestris Sw. is the most studied species, presenting more significant pharmacological potential. The chemical variability of EOs components was also investigated for this species. Caseria EOs have relevant pharmacological potential and must be further investigated and exploited.

Abstract

Four undescribed phenolic glycosides including three stilbene derivatives (1 and 3) and sodium salt of 3 (2), and a chalcone glycoside (4), together with thirteen known compounds (5–17) were isolated from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry. Their chemical structures were elucidated to be (Z)-gaylussacin (1), 6′′-O-galloylgaylussacin sodium salt (2), 6′′-O-galloylgaylussacin (3), 4′-O-[β-D-glucopyranosyl-(1→6)-glucopyranosyl]oxy-2′-hydroxy-6′-methoxydihydrochalcone (4), gaylussacin (5), pinosilvin 3-O-β-D-glucopyranoside (6), myricetin-3-O-(2′′-O-galloyl)-α-L-rhamnopyranoside (7), myricetin-3-O-(3′′-O-galloyl)-α-L-rhamnopyranoside (8), myricetin-3-O-α-L-rhamnopyranoside (9), quercitrin (10), myricetin-3-O-β-D-glucopyranoside (11), myricetin-3-O-β-D-galactopyranoside (12), quercetin 3-O-α-L-arabinopyranoside (13), myricetin-3-O-2′′-O-galloyl)-α-L-arabinopyranoside (14), (+)-gallocatechin (15), (−)-epigallocatechin (16), and 3,3’,4’-trimethoxyellagic acid 4-O-β-D-glucopyranoside (17) by the analysis of HR-ESI-MS, 1D and 2D NMR spectra in comparison with the previously reported data. Compounds 1–3, 5, and 6 significant inhibition of NO production in LPS-activated RAW264.7 cells, with IC₅₀ values ranging from 18.37±1.38 to 35.12±2.53 μM, compared to a positive control (dexamethasone) with an IC₅₀ value of 15.37±1.42 μM.

Abstract

A phytochemical investigation of the methanolic extract of the Macropanax membranifolius C.B. Shang leaves led to the isolation of three new flavans, (2R,3R)-4′-O-methylcatechin 5-O-β-D-glucopyranoside (1), (2S,3S)-4′-O-methylcatechin 5-O-β-D-glucopyranoside (2), (2S,3R)-4′-O-methylcatechin 5-O-β-D-glucopyranoside (3), one new triterpene glycoside 3-O-β-D-xylopyranosyl-(1→6)-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranosyl-oleanolic acid 28-O-β-D-glucopyranoside (4), together with nine known compounds (5-13). Their chemical structures were elucidated based on HR-ESI-MS, NMR spectroscopic data. The absolute configurations of compounds 1–3 were established by electronic circular dichroism (ECD) spectra. At concentration of 20 μM, compounds 1–13 showed the percentages of dead cell in the range of 2.14 % to 33.61 % against KB, HepG2, HL60, P388, HT29, and MCF7 cancerous cell lines by SRB assay.

Abstract

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H₂O₂-induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 μmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC₅₀ value of 3.06±2.40 μmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Abstract

A new polyaromatic metabolite, ent-herqueidiketal (1), and a new phenalenone derivative, epi-peniciherqueinone (2), along with twelve known compounds 3–14, were isolated from the fungus Penicillium herquei YNJ-35, a symbiotic fungus of Pulveroboletus brunneopunctatus collected from Nangunhe Nature Reserve, Yunnan Province, China. The structures of 1–14 and the absolute configurations of 1 and 2 were determined by their spectroscopic data or by their single-crystal X-ray diffraction analysis or optical rotation values. Compound 1 showed strong antibacterial activity against Staphylococcus aureus (ATCC 29213) with minimum inhibitory concentration (MIC) of 8 μg/mL. In the cytotoxicity assays, compound 1 showed weak inhibitory activity against breast cancer MCF-7 and mice microglial BV2 cells with half maximal inhibitory concentration (IC₅₀) of 17.58 and 29.56 μM; compound 14 showed stronger cytotoxicity against BV2 and MCF-7 cells with IC₅₀ values of 6.57 and 10.26 μM.

Abstract

Breast cancer is a malignancy that affects mostly females and is among the most lethal types of cancer. The ligand-functionalized nanoparticles used in the nano-drug delivery system offer enormous potential for cancer treatments. This work devised a promising approach to increase drug loading efficacy and produce sustained release of 5-fluorouracil (5-FU) and Ganoderic acid (GA) as model drugs for breast cancer. Chitosan, aptamer, and carbon quantum dot (CS/Apt/COQ) hydrogels were initially synthesized as a pH-sensitive and biocompatible delivery system. Then, CS/Apt/COQ NPs loaded with 5-FU-GA were made using the W/O/W emulsification method. FT-IR, XRD, DLS, zeta potentiometer, and SEM were used to analyze NP's chemical structure, particle size, and shape. Cell viability was measured using MTT assays in vitro using the MCF-7 cell lines. Real-time PCR measured cell apoptotic gene expression. XRD and FT-IR investigations validated nanocarrier production and revealed their crystalline structure and molecular interactions. DLS showed that nanocarriers include NPs with an average size of 250.6 nm and PDI of 0.057. SEM showed their spherical form, and zeta potential studies showed an average surface charge of +37.8 mV. pH 5.4 had a highly effective and prolonged drug release profile, releasing virtually all 5-FU and GA in 48 h. Entrapment efficiency percentages for 5-FU and GA were 84.7±5.2 and 80.2 %±2.3, respectively. The 5-FU-GA-CS-CQD-Apt group induced the highest cell death, with just 57.9 % of the MCF-7 cells surviving following treatment. 5-FU and GA in CS-CQD-Apt enhanced apoptotic induction by flow cytometry. 5-FU-GA-CS-CQD-Apt also elevated Caspase 9 and downregulated Bcl2. Accordingly, the produced NPs may serve as pH-sensitive nano vehicles for the controlled release of 5-FU and GA in treating breast cancer.