Current Chemical Biology - Online First

Fusarium oxysporum f. sp. Albedinis a telluric fungal pathogen commonly found in soils, is the causal agent of fungal vascular wilt of date palms in Moroccan oases. The infection by the pathogen leads to the death of the date palm after six months to two years, which causes enormous economic and environmental damage.

The framework of this paper is to determine the chemical composition of six essential oils using GC-MS and their antifungal activity on the mycelial growth of Fusarium oxysporum f. sp. Albedinis, as well as the molecular docking study to evaluate the inhibitory potential of fungal trypsin.

The essential oils were extracted from different parts of the plants (whole plant, flowers, and leaves) by steam distillation, and were identified using gas chromatography-mass spectrometry (GC/MS). The antifungal assay of the extracted essential oils and their main components was assessed using the direct contact method with the fungus at different concentrations; the obtained results were evaluated by calculating the minimum inhibitory concentration (MIC) of each essential oil, followed by an in-silico study of the major identified compounds for better understanding of the inhibitory potential against fungal trypsin activity.

The identification of the different bioactive compounds using GC-MS revealed that Rosmarinus officinalis Eo was characterized by eucalyptol 46.26%, camphor 10.03%, and β-pinene 6.63%; while Lavandula officinalis Eo was endowed by the presence of linalool 14.93%, camphor 14.11%, and linalyl acetate 11.17%. Furthermore, Artemisia herba alba was rich in 1,3,5-cycloheptatriene, 1,6-dimethyl- 36.44%, camphor 22.50%, and α-thujone 7.21%. While Eucalyptus globulus was rich in eucalyptol 74.32%, β-Cymene 11.41%, α-Pinene 6.96%. Finally, Mentha pepirita and Mentha pulegium were both characterized by the presence of D-limonene 20.15%, trans-carveol 19.59%, D-Carvone 14.96%, and pulegone (42.40%), 3-cyclopentene-1-ethanol, 2,2,4-trimethyl- (11.28%), 1,3,4-trimethyl-3-cyclohexenyl-1-carboxaldehyde (9.68%), respectively. Regarding the in vitro, all Eos from different plants exhibited pronounced antifungal effect. The MIC values recorded for E. globulus were MIC= 1.75 mg/L, M. pulegium and L. officinalis (MIC= 1.80 mg/L), and M. piperita (MIC= 1.90 mg/L). The strongest inhibition potential was associated with R. officinalis EO (MIC= 1.15 mg/L) and A. herba alba EO (MIC= 1.60 mg/L). As for the computational study performed camphor one of the bioactive compounds showed its ability to act against trypsin which could be considered a potential candidate against Fusarium oxysporum f. sp. Albedinis.

The studied essential oils from different medicinal and aromatic plants showed significant antifungal activity, probably due to the Camphor which could have an inhibitory effect on the Fusarium oxysporum f. sp. Albedinis trypsin. Further research should be conducted in vivo for a better understanding of the mechanism of action of these essential oils.

Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area.

This work aimed to synthesize some new analogs of carlina oxide by functionalizing the fifth position of the furan by different acyls groups using the Friedel-Crafts acylation approach, and then assess the in-vitro anti-inflammatory activity and in-silico alpha-amylase inhibition effect of carlina oxide and its synthetic analogs.

The new analogs were synthesized at room temperature using different anhydrides with the presence of boron trifluoride diethyl etherate (BF3Et2O) as acid catalyst. A protein denaturation assay was performed to evaluate the anti-inflammatory activity, while the molecular docking study was conducted using the Molecular Operating Environment (MOE) with three types of alpha-amylase sources: human salivary, pancreatic alpha-amylase and Aspergillus oryzae alpha-amylase (PDB: 1Q4N, 5EMY, 7P4W respectively).

A total of four analogs of carlina oxide were obtained in yields of 60-7% and then identified with ¹H and ¹³C NMR analysis. Additionally, analog 1 exhibited the better anti-inflammatory effect with IC50 of 0.280 mg/mL. However, the in-silico study showed that all the synthetic analogs have different interactions with human salivary alpha-amylase (1Q4N) and other interactions with 5EMY and 7P4W.

The new analogs of carlina oxide can have the potential to serve as an alternative agent for alpha-amylase inhibition, contributing to the reduction of postprandial hyperglycemia.

Chalcones have been demonstrated to contain numerous therapeutic qualities in recent years, such as antibacterial, antiviral, anti-ulcerative, antioxidant, anti-inflammatory, antihyperglycemic, antimalarial, antitubercular, analgesic, antiplatelet, and anticancer activities.

To explorethe synthesis, docking, and characteristics of chalcones as antibacterial and anthelmintic compounds.

The chalcone derivatives (3a-3k) and (6l-6v) were synthesized via two selective different reactions, based on the Claisen-Schmidt reaction. All synthesized compounds were evaluated for their antibacterial activity using an in vitro cup-plate method, and their anthelmintic activity was assessed using an in vitro earthworm paralysis and death assay. To validate these findings, conducted molecular docking experiments between the dihydrofolate reductase receptor (PDB ID: 4LAE) and the synthesised compounds (3a-3k) and (6l-6v) to determine catalytic interactions.

Compound 6(n) exhibited the greatest efficacy in biological in vitro activity against S. aureus compared to all other compounds examined. Compound 6(o) exhibited substantial efficacy against P. posthuma and E. coli. Emphasizing these findings, the compounds 3(a), 3(g), 3(i), 6(n), and 6(o) demonstrated hydrogen bond interactions with certain amino acid residues of the receptor, including THR 122, ASN 18, ASN19, GLN 96, SER 50, and ALA 8, during molecular docking.

The study results showed that the synthesised derivative (E)-1-(napthalen-2-yl)-3-(4-(trifluoromethoxy)phenyl)prop-2-en-1-one 6(n) had beneficial antibacterial properties against S. aureus, while derivative (E)-1-(Napthalen-2-yl)-3-(4-trifluoromethyl)phenyl)prop-2-en-1-one 6(o) exhibited antibacterial activity against E. coli and anthlelmintic activity against P. posthuma.

Phosphorylated α-Synuclein (α-Syn) is present in relatively small levels in normal human brains, but nearly all of the α-Syn in the Lewy bodies (LBs) that collect in the nigrostriatal region in the brain of Parkinsons disease patients is phosphorylated on serine 129 (pS129). Earlier studies suggested that mimicking phosphorylation at S129 may have an inhibitory effect on α-Syn aggregation and thus control α-Syn neuropathology. Although phosphorylation at S129 is associated with α-Syn inclusion in synucleinopathies, the mechanisms by which this post-translational modification (PTM) influences aggregation and contributes to LB illness in the brain are yet to be understood.

This research aims to study the effect of phosphorylation (pS129) on the conformational dynamics of membrane-bound α-Syn using Molecular Dynamics (MD) simulations.

Using MD simulations, this computational study has demonstrated the effect of PTM on the conformational dynamics of pS129 α-Syn and its lipid membrane association. To better understand the impact of pS129 on the aggregation of the α-Syn structure monomer with recent atomic details, we have examined the MD trajectories, conducted a salt-bridge interaction study, Principal Component Analysis (PCA), and intra and inter-molecular hydrogen bond analysis.

The conformational structure of pS129 α-Syn was observed from the MD trajectory analysis to be stable throughout the simulation, with higher compactness and reduced flexibility. The stability of the structure of pS129 α-Syn was also evaluated by 2-D and 3-D principal component analysis followed by a free energy landscape plot showing the global minima. The conformational snapshots and Ramachandran plot showed the absence of α-strands in the α-Syns Non-Amyloid Component Region (NAC) (71–82), which is necessary for aggregate formation.

Further, the intermolecular hydrogen bonds analysis indicates that the NAC region is not embedded into the lipid bilayer and has limited association with the other regions of the protein. Our findings reveal salient features of pS129 modifications that inhibit α-Syn aggregation.

Leukemic stem cells are considered to be the main cause of treatment failure and disease recurrence due to their resistance to most common therapies. Apoptosis induction is one of the highly effective methods for treating cancer. Ciprofloxacin is among the compounds whose antitumor effects have been confirmed.

In this study, we investigated the anti-proliferative effect and induction of apoptosis by one of the derivatives of this family called 1-Cyclopropyl-6-fluoro-7-[4-(2-{[(1R,2S,5R)- 2-isopropyl-5-methylcyclohexyl]oxy}-2-oxoethyl)-piperazin-1-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (ICH-CP) on NB4 cell line as an in vitro model of Acute promyelocytic leukemia (APL). NB4 cells were treated using the ICH-CP combination in various concentrations.

The viability of NB4 cells was evaluated by MTT assay, and their morphology of apoptosis was examined by fluorescence microscopy. Flow cytometry and Annexin V/PI staining were used to quantify apoptosis. Finally, the expression of three genes, Bax, Bcl-2, and Survivin was inquired by real-time PCR.

According to the results, ICH-CP was able to destroy about 60% of NB4 cells in a dose and time-dependent manner. Light microscopy and fluorescence microscopy studies on treated cells confirmed the induction of apoptosis. Also, the real-time PCR analysis showed that ICH-CP induces apoptosis in the NB4 cell line via the down-regulation of Survivin and Bcl-2, in contrast to the up-regulation of the Bax gene.

Based on the present data, it seems that the novel compound can be a good candidate for the treatment of acute myeloid leukemia. Furthermore, it is recommended to evaluate the qualification of ICH-CP as an adjunctive agent for other cancer cell lines.

Numerous natural products have been successfully developed for clinical use in the treatment of human diseases in almost every therapeutic area.

This work aimed to assess the in-vitro and in-silico α-amylase inhibition activities of carlina oxide and aplotaxene, isolated from the roots of Carthamus caeruleus and Rhaponticum acaule respectively.

The essential oil from C. caeruleus roots was obtained using a Clevenger-type apparatus, and the hexanoic extract from the roots of R. acaule was obtained through maceration. Major components of each plant were separated via column chromatography. The in-vitro α-amylase inhibition activity was evaluated using porcine pancreatic α-amylase, while the molecular docking study was conducted using the Molecular Operating Environment (MOE) with three types of α-amylase: human salivary, pancreatic α-amylase and Aspergillus oryzae α-amylase (PDB: 1Q4N, 5EMY, 7P4W respectively).

The in-vitro α-amylase inhibition results for the essential oil, the hexanoic extract, carlina oxide and aplotaxene showed that carlina oxide exhibited significant activity with IC50 of 0.42 mg/mL. However, the in-silico study showed no interaction between aplotaxene and the three α-amylase enzymes, whereas carlina oxide demonstrated one pi-cation interaction with 5EMY with the amino acid TYR 62 at a distance of 4.70 Å and two pi-H interactions with 7P4W with the amino acid LYS 383 at distances of 4.31 and 4 .03 Å.

In conclusion, carlina oxide has the potential to serve as an alternative agent for α-amylase inhibition, contributing to the reduction of postprandial hyperglycemia.

Obesity is a serious chronic metabolic disease impairing health damaging many organs such as kidneys and muscles. Ovothiol-A (Ovo-A) has been found to keep the redox balance normal in sea urchins indicating its antioxidant characteristics.

This study aims to investigate the protective effects of Ovo-A on kidneys and muscles in obese rats.

In-silco studies were performed on lactate dehydrogenase (LDH) and creatine kinase (CK) with Ovo-A to compute their binding affinities. Obesity was induced by high-fat diet (HFD) for 4 weeks. Wistar rats were used in this study as 6 rats per group as control, HFD, Ovo-A (200 and 400 mg/Kg, p.o) groups.

Docking results have revealed that Ovo-A has affinities to bind to LDH (-8.5 kcal/mol) and CK (-17.7 kcal/mol). Ovo-A reduced the levels of uric acid, urea, creatinine, LDH, CK, malondialdehyde (MDA), and nitric oxide (NO), while increasing the levels of glutathione (GSH), catalase (CAT), and glutathione-S-transferase (GST). Histopathological investigations have revealed that Ovo-A restored the renal and muscular structure.

The current study showed that Ovo-A has a protective effect on kidneys and muscles in obese rats. Ovo-A enhances renal and muscular functions by inhibiting LDH and CK activities and improving the antioxidant system. Ovo-A is more effective in the high dose.