Journal of the Chilean Chemical Society

Unveiling Molecular Interactions: Coumarin Derivatives and Dengue Virus Protein Targets

Hezha O. Rasul — 2024-10-06

Dengue is a virus-borne disease that causes fever, headaches, nausea, muscle pain, and other symptoms. The majority of cases are mild, but there are severe forms of Dengue fever like hemorrhagic fever and Dengue shock syndrome, which can be life-threatening. Severe cases may cause breathing difficulties, excessive bleeding, abdominal pain, vomiting, fluid build-up, and extreme fatigue. This highlights the need for widespread knowledge and health care interventions in areas where Dengue is prevalent. . The objective of this work was to use virtual screening to explore how coumarin derivatives bind to Dengue virus protein targets and their affinities to ligands and receptors. Molegro Virtual Docker allowed for structure based virtual screening by taking advantage of the importance of protein like interactions in drug development. The docking studies provide a basis to understand the early stages of ligand-receptor interactions and guide further research. In order to further investigate the complex atomic-level behaviours of proteins and biomolecules in the fields of molecular biology and drug discovery, we performed estimations using molecular dynamics simulations (MD) and MM-GBSA calculations. The evaluation encompassed the examination of antiviral activity, drug-likeness, ADMET features, and quantum chemistry techniques of selected compounds. This comprehensive analysis aimed to explore the molecular interactions between coumarin derivatives and Dengue virus protein targets from multiple perspectives. The findings indicate that (S)-6-hydroxy-7-(5-hydroxy-3,7-dimethyl-2,6-octadienyloxy)coumarin demonstrates the greatest binding affinity among the chemicals that were examined. It is then followed by 6-hydroxy-7-(7-hydroxy-3,7-dimethyl-2,5-octadienyloxy)coumarin, wedelolactone, and medicagol. These findings have the potential to enhance the progress of creating new antiviral drugs that are more effective in treating Dengue virus infections, by utilising various artificial intelligence methods.

Improvement of Head-to-Tail RGD peptide Cyclization Efficiency Combining Low Temperature and Lithium Chloride

Adriana Gauna — 2024-10-06

RGD-containing peptides (linear and cyclic) have been developed to target some types of cancer cells through interaction with the αvβ3 Integrin. Due to their reduced conformational freedom, cyclic peptides exhibit improved metabolic stability and binding affinity/specificity to their molecular targets. However, macrocyclization is considered a significant synthetic challenge that is affected by the ring size, peptide sequence, and reaction conditions, making tetra- and pentapeptides more difficult to cyclize. In this work, we report some optimized cyclization conditions for the obtention of a cyclic RGDfK peptide that combine the use of low reaction temperature and the addition of LiCl, a combination not yet reported that resulted in a reduction of the formation of oligomers and an improvement of the cyclization efficiency.

FIRST REPORT ON THE BIOLOGICAL ACTIVITIES, MOLECULAR DOCKING AND STUDY OF THE TOXICITY OF TWO OLEORESINS AS WELL AS THEIR MAIN CONSTITUENTS

Meriem Elkolli — 2024-10-06

The objective of this work was to evaluate the in vitro and in silico antibacterial, anti-inflammatory and antioxidant activities of two oleoresins; Myrrh and Pine resin used in the Algerian traditional pharmacopoeia. The antibacterial effect of oleoresins was evaluated by the agar diffusion test against three bacterial strains; E. coli (ATCC 25922), S. aureus (ATCC 25923) and P. aeuroginosa (ATCC 27853). The antioxidant activity was assessed using DPPH method and the protein inhibition denaturation test was used to evaluate the anti-inflammatory efficacy. Resins main compounds were docked in silico against the bacterial tyrosyl-tRNA synthetase using the Autodock Tools 1.5.7 software. This study was carried out to determine their modes of binding with the active residues of this molecular target enzyme of antimicrobial agents. Molinspiration Cheminformatics and SwissADME online tools were used to predict physicochemical and pharmacokinetic parameters while OSIRIS Property Explorer online tools were used to predict toxicity risks. The results show that the Myrrh was effective against E. coli and S. aureus (17 mm) and that the Pine resin was similarly effective against E. coli (11 mm) and S. aureus (10 mm), but P. aeruginosa was completely resistant. The antioxidant test showed that both oleoresins had considerable ability to reduce the DPPH, with good IC₅₀ of 0.49 ± 0.13 and 0.53 ± 0.06 mg/ml, respectively, compared to the BHT (0.89 ± 0.45 mg/ml). Both oleoresins had a remarkable anti-denaturation effects. The data of in silico studies revealed that all phytocompounds fit into the active pocket of the target enzyme and the binding energies ranged between -10.06 (Dehydroabietic acid) and -4.3 kcal/mol (D-glucuronic acid). The toxic and pharmacokinetic characteristics are, mostly, satisfying except for some compounds which have shown toxic effects, in particular Limonene, 4-allylanisole and Vanillin. We conclude that the extracts and their primary phytocompounds can enhance the antibacterial, antioxidant, and anti-inflammatory existing drugs without side effects.

Synthesis of novel lipoic acid derivatives

Juan Pablo González-Gutiérrez — 2024-10-06

Lipoic acid is a naturally occurring compound involved in biological processes with special reactivity due to its 1,2-dithiolane ring. The novel ALA derivatives were synthesized using the Steglich esterification in mild conditions and then concentrated and neutralized with yields of 45.1 to 81.2%.

COMPARATIVE DETERMINATION AND HEALTH RISK ASSESSMENT OF CADMIUM, CHROMIUM AND COPPER IN WILD AND AQUACULTURED CLARIAS GARIEPINUS, OREOCHROMIS NILOTICUS AND MICROPOGONIAS UNDULATUS SOLD IN GWAGWALADA AREA COUNCIL, FCT - NIGERIA.

EPHRAIM DALLATU — 2024-10-06

This study assesses the levels of copper (Cu), chromium (Cr), and cadmium (Cd) in wild and aquacultured Oreochromis niloticus (Tilapia), Micropogonias undulatus (Croaker), and Clarias gariepinus (Catfish) that are sold in Gwagwalada Area Council, Federal Capital Territory, Nigeria. A random sample of 500 g of each species of fish was taken from the markets in Dobi, Gwagwalada, and Zuba. The labels for the composite samples were: aquacultured catfish (Acf), aquacultured tilapia (Atf), aquacultured croaker (Acrf), wild catfish (Wcf), wild tilapia (Wtf), and wild croaker (Wcrf). Oven-dry weight and furnace procedures were used to determine the contents of moisture and ash. Wcf, Wtf, and Wcrf had moisture contents of 4.25±0.354%, 5.25±0.453%, and 4.50±0.000%, respectively, according to the results, whereas Acf, Atf, and Acrf had moisture contents of 7.01±0.230%, 7.12±0.234%, and 6.70±0.210%, respectively. For Wcf, Wtf, and Wcrf, the ash content was 1.75±0.354%, 1.64±0.231%, and 1.48±0.213%, respectively. The possible health concerns linked with the consumption of these heavy metals were determined by measuring and comparing their concentrations. The results show that various fish species accumulate metals at different rates, which could have an impact on public health because extended exposure to these toxins can cause health problems.

Synthesis and application of mixed spinel Mn0.4Cd0.6Cr2S2Se2: Structural, magnetic, and electrochemical sensing properties

Silvana Moris — 2024-10-06

Herein we report the solid synthesis, structural characterization, magnetic behavior, and electrochemical sensing properties of Mn_0.4Cd_0.6Cr₂S₂Se₂. Single‐crystal X‐ray diffraction analysis showed that Mn_0.4Cd_0.6Cr₂S₂Se₂crystallizes in a spinel‐type structure. Powder X-ray diffraction patterns and Rietveld refinement data revealed that this selenide phase is consisted of cubic Fdm space group. Magnetic field cooling (MFC) measurements indicated an enhancement in ferromagnetic interactions relative to the ferrimagnetic compound Mn_0.4Cd_0.6Cr₂S₄, which can be attributed to the substitution of sulphur by selenium. The electrochemical response of modified glassy carbon electrodes with Mn_0.4Cd_0.6Cr₂S₂Se₂was increased, the peak current is increased 4-fold, from 20.15 µA to 83.52 for GC, and GC-Mn_0.4Cd_0.6Cr₂S₂Se₂ respectively by differential pulse voltammetry, and thus it could be used to design an electrochemical sensor to quantify nitrocompounds, considered pollutants and toxic agents for humans, plants, and animals.

First report on antioxidant and antimicrobial activities of essential oil of Persea americana from Algeria

NOUARA AIT MIMOUNE — 2024-10-06

The present investigation describes the chemical profile and biological activities of Persea americana essential oil (EO) isolated by hydrodistillation. The chemical composition was determined using Gas Chromatography-Mass Spectrometry (GC–MS). The main compounds found were represented by estragole (65.5%) and methyleugenol (10.94%). The antibacterial activity was evaluated against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Results revealed the effectiveness of the essential oil on both Gram-positive and Gram-negative bacteria. The screening of antifungal activity was performed using poisoned food and broth-microdilution assays. P. americana EO was capable of inhibiting the mycelial growth of all tested fungi, with Cladosporium sp. and Altenaria sp. being the most sensitive species. The DPPH test performed to determine the antioxidant activity showed a low IC₅₀ value of 0.22 mg/mL. Overall, P. americana EO proved to be an effective antimicrobial and antioxidant agent, that could be used as a natural perspective to control foodborne pathogens and lipid peroxydation.

Evaluation of microwave-assisted acid/oxidant digestion method for the detection of polyethylene microplastics in Merluccius Gayi fish by Nile Red fluorescent staining and image analysis

CRISTOFHER FERRADA — 2024-10-06

This study proposes a new method for the determination of polyethylene in Merluccius Gayi by microwave digestion, Nile Red fluorescent staining, mobile phone camera and image analysis.

We have demonstrated that lyophilization of the sample is an unnecessary step in the process of determining polyethylene microplastics, obtaining recoveries close to 65% and generating sample losses. Furthermore, a method for matrix reduction is validated using direct raw sample digestion with 9/1 HNO₃/H₂O₂microwave-assisted digestion achieving recoveries of over 98% for microplastics.

Polyethylene fluorescent color obtained was a bright yellow, which allowed it to be distinguished from micro-particles of polystyrene, polypropylene, polyvinyl chloride, and polyethylene terephthalate easily to the naked eye. Additionally, it was possible to train artificial intelligence to perform this selective identification through image analysis.

Computational Design and Toxicity Prediction of Oxazole Derivatives Targeting PPARγ as Potential Therapeutics for Diabetes Mellitus in Compare to Rosiglitazone and Pioglitazone

Mohammad Rashid Rashid — 2024-10-06

The goal of this research is to investigate new oxazole derivative from designed series (A1-7; B1-8 & C1-8) in order to find new drug molecules for treatment of Diabetes Mellitus (DM). The PPAR receptor was chosen as the target of molecular docking investigations, which were executed using PyRx software. In silico analyses, including physicochemical properties, drug score, drug likeness, solubility, and toxicity prediction, were conducted using software such as Swiss ADME, Osiris property explorer, Lipinski filter and Toxtree method. All molecules passed the Lipinski rule with the zero violations and synthetic score was also found to be in the easy limit. All ligands showed drug score values ranging from 0.11 to 0.9 (no negative value). Compounds A6, C2, C5, C6, C7 and C8 were shown drug score from 0.91 to 0.80, which is closer to 1 and therefore considered as druggable ligands, when compared with the standard drug, Rosiglitazone and Pioglitazone also found non-toxic. All compounds shown logP values between -0.25 to 4.58. The RMSD value of receptor and receptor-ligand complexes was analyzed, and it revealed the stability of binding interactions and remained stable throughout the simulation. Compound C8 was found highest RMSD score (67.34Å) in compare to other compounds and standard drug Rosiglitazone (64.31Å). The TPSA were found within the range 35.26 to 128.60 and MR also were in the range 32.21-113.62. Compounds were found to be non-substrate for p glycoprotein except C4, high GIA% (>90%), also displayed negative permeability across the BBB, and most of compounds were found inhibitor of CYP 1A2 and CYP 2C19 and non-inhibitor of CYP 2C9, CYP 2D6 and CYP 3A4. Compound C5 was exhibited higher drug score (0.91), bioactivity score and revealed good drug relevant properties, ADME and no toxicity profile in compared to other ligands and standard drugs. The most active compound of the series was found C5 and C8 therefore further studies on this compound continue in our research laboratory to acquire more information about SAR and QSAR. Finally, it is conceivable that further derivatization of these compounds could result in obtaining more selective lead compounds.