Curcumin is the most effective therapeutic agent and has anticancer activity. But due to the diketone moiety, it has a weak pharmacokinetic profile. The aim is to identify the best candidate from the designed mono-carbonyl curcumin derivatives that bind to the T790M mutated crystal structure. Three distinct EGFR crystal structures, including the wild-type (PDB: 1M17 and 4I23) and T790M mutant (PDB: 6LUD), were subjected to comparative molecular docking. Focusing on the T790M mutated crystal structure (6LUD), NME 3 was then studied for molecular dynamics. Designated derivatives were found to have good ADMET properties. Among all the New Molecular Entities, NME1, 2, and 3 were found to have good binding affinity towards 1st, 2nd, and 3rd generation EGFR crystal structures and a greater dock score than standard curcumin. Therefore, NME 3 was further studied for molecular dynamics, and results were compared with those of the co-crystallised ligand S4 (Osimertinib). It was found that the RMSD (1.8 Å), RMSF (1.45 Å ), and radius of gyration (4.87 Å) values of NME 3 were much lower than those of S4 (Osimertinib). All this confirms that our designed NME 3 is more stable than reference S4 (Osimertinib).

One of the endangered plant species in Saint Catherine protectorate is Hypericum sinaicum Boiss which is endemic to Egypt, Jordan, and Saudi Arabia. The fungus-host relationship can assist in the investigation of bioactive compounds produced by H. sinaicum paving the way for economic and medicinal implications. Therefore, a comprehensive metabolic approach via MS and chemical analysis was used to track and compare metabolites from H. sinaicum and Aspergillus foetidus var. pallidus, the endophytic fungus, with Hypericum perforatum. Metabolomics analysis revealed the presence of 25 metabolites distributed among samples and the discovery of new chemotaxonomic compounds, i.e., phloroglucinols and xanthones, allowing the discrimination between species. A. foetidus extract is considered a reliable source of furohyperforin and naphthodianthrone derivatives. In conclusion, using A. foetidus as an in vitro technique for producing potential phytoconstituents was cost effective, having easier optimization conditions and faster growth with fewer contamination rates than other in vitro methods.

In this study, the composition of the volatile oils obtained from the fruits of 8 Ferulago species (Ferulago cassia Boiss., F. isaurica Peşmen, F. humilis Boiss., F. macrosciadia Boiss. & Balansa, F. setifolia K.Koch, F. silaifolia (Boiss.) Boiss., F. syriaca Boiss., F. trojana Akalın & Pimenov) growing naturally in Turkey were examined by means of GC/MS and GC-FID and α-pinene was determined to be present in the fruits of four species along with other monoterpenes as major components. Principal Component Analyses (PCA) and Hierarchical Cluster Analysis (HCA) was performed, utilizing ten major components in the eight essential oils. Also, a Venn diagram was used to demonstrate chemotaxonomical variations in the composition of the essential oils of eight Ferulago species.

Abstract

In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure–activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.

Abstract

Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85–94 %) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (¹H-NMR, ¹³C-NMR), and High-Resolution Mass Spectroscopy (HR-MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the K_i values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α-Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.

Abstract

Gnetum latifolium var. funiculare Markgr. is a medicinal plant and widely distributed in mountainous areas of Vietnam. Phytochemical investigation on the trunks of this plant afforded eight stilbene derivatives (1–8) including for new compounds (1–4). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Among the isolates, compounds 1–3 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with the IC₅₀ values ranging from 46.81 to 68.10 μM, compounds 4 and 6 showed weak effects with the IC₅₀ values of 96.57 and 79.46 μM, respectively, compared to that of the positive control compound, dexamethasone (IC₅₀ 14.20 μM).

Abstract

Syzygium aromaticum is used in traditional and modern medicine for its various and outstanding pharmacological properties. Here, we studied the chemical composition of hexane extract and non-polar fractions (NPF) obtained from the maceration and fractionation of clove buds, in order to evaluate their in vitro antimycobacterial activity, as well as their contribution against efflux pump (EP) resistance through molecular docking experiments. The gas chromatography-mass spectrometry (GC–MS) analysis of the volatile profiles revealed the presence of eugenol, followed by eugenyl acetate, and β-caryophyllene as common major compounds. According to Resazurin microtiter assay (REMA), Mycobacterium tuberculosis H₃₇Rv strain was sensitive to all volatile samples at concentration range between 10 and 100 μg/mL. The NPF of ethanol extract was the best inhibitor with a MIC=10 μg/mL. The in silico study revealed a strong binding affinity between eugenol and Mmr EP protein (−8.1 Kcal/mol), involving two binding modes of hydrogen bond and π-alkyl interactions. The non-polarity character of clove volatile constituents, and their potential additive or synergistic effects could be responsible for the antimycobacterial activity. In addition, these findings suggest the benefic effect of eugenol in the management of mycobacterium drug resistance, whether as potential inhibitor of Mmr drug EP, or modulator during combination therapy.

The structure of the pyridine-based Schiff base compound containing the propargyl group was characterized by NMR spectroscopy. Binding of compound 2 with double-stranded fish sperm DNA (Fsds-DNA) was investigated using viscosity measurement studies and UV-Vis and fluorescence spectral techniques. Binding of compound 2 with Fsds-DNA results in minor hypochromism with no change in absorption maxima and fluorescence quenching with almost no shift in emission maxima, which can be attributed to the groove-binding mode of the interaction. The binding constant was found to be 4.7 x 104 M-1. The Fsds-DNA viscosity measurement, KI quenching and NaCl quenching studies and the competitive interaction between compound 2 and ethidium bromide with DNA confirm the proposed binding mode. In addition, interactions between compound 2 and the DNA double helix were analysed by molecular docking study in order to determine the binding mode and binding affinity. As a result of molecular docking, the binding affinity of the 2-DNA complex, which has the most stable conformation -8.10 kcal/mol and it is located in its minor groove. In addition, molecular docking and ADME studies for compound 2 were also performed.

The aim of this work is to optimise the antibacterial activity of essential oils (EOs) from Eucalyptus camaldulensis (ECEO), Mentha pulegium (MPEO) and Rosmarinus officinalis (ROEO) plants against Salmonella spp. and Escherichia coli. The qualitative antimicrobial effect was assessed using the disc diffusion method, the broth microdilution method was used to determine the minimum inhibitory concentrations (MIC). Polynomial models were created using an augmented centroid simplex mixture design to highlight the synergy of EOs. The results show a significant antibacterial effect of ECEO and MPEO against both bacterial strains, with inhibition zones (IZs) of 13 and 12 mm respectively against E. coli, and 13 and 11 mm against Salmonella spp. The latter strain showed a MIC of 0.625% (v: v) by the ECEO, while E. coli exhibited a MIC of 0.0781% (v: v). The binary combinations of essential oils display a synergistic effect, the proportions of the optimum EOs in the mixture giving the lowest MICm were of the order of 50.51% ECEO and 49.49% ROEO against Salmonella spp. and around 50% MPEO and 50% ECEO against E. coli. These results indicate the effectiveness of binary combinations EOs against resistant bacterial strains and suggest their importance in bacterial infections treatment.

In this work, the design, synthesis and mechanistic studies of a novel pyrazole-based benzofuran derivatives 1-8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A-549, human-derived colorectal adenocarcinoma HT-29, breast adenocarcinoma MCF-7 cells as well as mouse fibroblast 3T3-L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose-dependent anti-proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti-proliferative activity with an IC50 value of 7.31 µM and the highest selectivity (15.74) on MCF-7 cells. Flow cytometry results confirmed that the cytotoxic power of the compound 2 on MCF-7 cells is closely related to the mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase-3 via in-silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute a preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.