Current Chemical Biology - Volume 18, Issue 4, 2024

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.

The use of lacatomtom (LTT), a psychoactive mixture of tomtom (TT) candies with lacasera (LC) beverage, has recently increased among young Nigerians and Africans. There isn't much scientific study on the constituent and effects of this psychoactive substance.

Herein, LTT was chemically-profiled using GCMS analysis, and the toxicological effects were examined in albino rats. In vivo experiment consists of five groups of six rats each (group 2 - LTT ad libitum; groups 1, 3, & 4 - TTT, TT, LC (1 mL) mg/mL kg/body weight once/day respectively, group 5 - distilled water ad libitum). Identified constituents were examined against human monoamine oxidase (hMOA) and human catechol O-methyltransferase (hCOMT) using in silico methods.

Forty-seven chemical compounds were identified. Ad libitum intake of LTT elevated plasma alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, total cholesterol, and LDL-cholesterol levels. The docked poses, binding scores, and interactions with amino acids informed the selection of (4-Methoxymethoxy-hex-5-ynylidene)-cyclohexane (MM) (-9.4 kcal/mol) and 3-(hydroxyphenylmethyl)-3,4-dimethyl-1-phenylpentan-2-one (HP) for hCOMT (-9.4 kcal/mol), while propionylcodeine (-10.1 kcal/mol) and HP (-8.9 kcal/mol) for hMOA. Top-docked compounds (TDC) demonstrated the potential to permeate the blood-brain barrier. TDC was predicted to be a positive substrate of the P-glycoprotein and presents inhibitory potential for cytochrome P450 descriptors. HP was mutagenic and could induce human hepatotoxicity and drug-induced liver injury, while propionylcodeine had a human hepatotoxic prediction.

The present study, for the first time, confirmed the potential toxicity of lacatomtom to the liver, kidney, heart, and central nervous system supported by the identified top-docked compounds regarded as potential psychoactive constituents of hMOA and hCOMT.

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 acyl groups using the Friedel-Crafts acylation approach. The synthetic analogs and carlina oxide were then assessed for their in-vitro anti-inflammatory activity and in-silico alpha-amylase inhibition effect.

The new analogs were synthesized at room temperature using different anhydrides with the presence of boron trifluoride diethyl etherate (BF3-Et2O) as an acid catalyst. A protein denaturation assay was performed to evaluate the anti-inflammatory activity, while the in-silico study was conducted using the Molecular Operating Environment (MOE) with different types of alpha-amylase sources, such as 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 a better anti-inflammatory effect with an 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 have the potential to serve as an alternative agent for alpha-amylase inhibition, contributing to the reduction of postprandial hyperglycemia.

Gallic acid (GA), a natural phenolic acid, has been reported as an antitumor agent in various cancer cells. Although some mechanisms, such as apoptosis, are well known, the details of other mechanisms, such as their pro-oxidant and autophagy activity, are still considerable.

The pro-oxidative activity and anti-proliferative activity of GA on HEK 293 and HepG2 cells were measured in the absence and presence of exogenous Cu (II) and Fe (II). Furthermore, colony forming, ROS generation, apoptosis induction, autophagy and mitochondrial membrane potential (MMP) were examined.

HepG2 cells treated with GA + Cu (II) significantly reduced cell viability (p <0.001). GA +Cu (II) induced morphological changes in HepG2 cells and stimulated apoptotic cell death. Moreover, GA +Cu (II) triggered the mitochondrial-dependent apoptotic pathway by increasing intracellular ROS levels and disrupting MMP. Furthermore, GA+ Cu (II) significantly reduced the Plating Efficiency and Surviving Fraction while increasing autophagic vacuoles in the HepG2 cells.

According to our results, GA played a pro-oxidant role in the presence of Cu (II), triggered apoptosis by increased ROS and disruption of MMP. This combination also induced autophagy in HepG2. These effects hold promise for future anticancer research.