Antioxidant and antibacterial activities of 5-mercapto(substitutedthio)-4-substituted-1,2,4-triazol based on nalidixic acid: A comprehensive study on its synthesis, characterization, and In silico evaluation.

This study introduces a series of novel Alkyl thio-1,2,4-triazole (4a-p) and mercapto-1,2,4-triazole (3a-d) compounds derived from nalidixic acid. The synthesis was streamlined, involving interactions between nalidixic acid hydrazide and various isothiocyanates to yield cyclic and alkyl(aryl) sulfide compounds, characterized using 1H NMR, 13C NMR, IR, and elemental analysis. Antioxidant capabilities were quantified through DPPH and ABTS assays, highlighting significant potential, especially for compound 3d, which demonstrated an ABTS IC50 value of 0.397 µM, on par with ascorbic acid (IC50 = 0.87 µM). Antibacterial efficacy was established through MIC assessments against a broad spectrum of Gram-positive and Gram-negative bacteria, including Candida albicans. Compounds 3b, 4e, 4h, 4j, 4i, 4m, and 4o showed broad-spectrum activity, with 4k and 4m exhibiting pronounced potency against E. coli. Molecular docking studies validated the antibacterial potential, with compounds 4f and 4h showing high binding affinities (docking scores of -9.8 and -9.6 kcal/mol, respectively), indicating robust interactions with the bacterial enzyme targets. These scores underscore the compounds' mechanistic basis for their antibacterial action and support their therapeutic promise. Furthermore, compounds 3b, 4i, and 4m, identified through drug-likeness and toxicity predictions, were highlighted for their favorable profiles, suggesting their suitability for oral antibiotic therapies. This comprehensive study, blending synthetic, in vitro, and in silico approaches, emphasizes the triazole derivatives' potential as future candidates for antibiotic and antioxidant applications, particularly spotlighting compounds 3b, 4i, and 4m due to their promising efficacy and safety profiles.

Anticancer, antioxidant, and antibacterial activity of chemically fingerprinted extract from Cyclamen persicum Mill.

In the last few decades, researchers have thoroughly studied the use of plants in Palestine, one of them is Cyclamen persicum Mill. (C. persicum). Cyclamen persicum has been historically cultivated since the 1700s due to its tuber. The tuber is known to stimulate the nasal receptors, thus triggering the sensory neurons. Cyclamen persicum has anti-inflammatory effects, reduces cholesterol levels, treats diabetes, and inhibits tumor growth. In this respect, in-vitro examination of antibacterial and anticancer activities and antioxidative potency of C. persicum ethanolic extract were evaluated. The antioxidative potency of the extracted plant material was determined spectrophotometrically using the DPPH free radical scavenging method and the HPLC-PDA method to evaluate its total phenolic content (TPC) and total flavonoid content (TFC). The experimental results revealed weak antibacterial activity of C. persicum extract against both gram negative (E. coli) and gram positive (Streptococcus aureus and S. aureus) bacterial strains, with the zones of inhibition found to be less than 8 mm. On the other hand, powerful activity against MCF7 breast cancer as well as HT29 colon cancer cell lines was obtained. The findings also revealed potent inhibition of free radicals and the presence of maximal levels of natural products such as phenolic compounds and flavonoids, which supportits biological activities and powerful ability to scavenge free radicals. HPLC results showed the presence of numerous flavonoid and phenolic compounds such as rutin, chlorogenic acid, kaempferol, trans-cinnamic acid, quercetin, sinapic acid, and p-coumaric acid.

Diosgenin and Monohydroxy Spirostanol from Prunus amygdalus var amara Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach.

Cancer continues to be leading cause of death globally, with nearly 7 million deaths per year. Despite significant progress in cancer research and treatment, there remain several challenges to overcome, including drug resistance, the presence of cancer stem cells, and high interstitial fluid pressure in tumors. To tackle these challenges, targeted therapy, specifically targeting HER2 (Human Epidermal Growth Factor Receptor 2) as well as EGFR (Epidermal Growth Factor Receptor), is considered a promising approach in cancer treatment. In recent years, phytocompounds have gained recognition as a potential source of chemopreventive and chemotherapeutic agents in tumor cancer treatment. Phytocompounds are compounds derived from medicinal plants that have the potential to treat and prevent cancer. This study aimed to investigate phytocompounds from Prunus amygdalus var amara seeds as inhibitors against EGFR and HER2 enzymes using in silico methods. In this study, fourteen phytocompounds were isolated from Prunus amygdalus var amara seeds and subjected to molecular docking studies to determine their ability to bind to EGFR and HER2 enzymes. The results showed that diosgenin and monohydroxy spirostanol exhibited binding energies comparable to those of the reference drugs, tak-285, and lapatinib. Furthermore, the drug-likeness and ADMET predictions, performed using the admetSAR 2.0 web-server tool, suggested that diosgenin and monohydroxy spirostanol have similar safety and ADMET properties as the reference drugs. To get deeper insight into the structural steadiness and flexibility of the complexes formed between these compounds and theEGFR and HER2 proteins, molecular dynamics simulations were performed for 100 ns. The results showed that the hit phytocompounds did not significantly affect the stability of the EGFR and HER2 proteins and were able to form stable interactions with the catalytic binding sites of the proteins. Additionally, the MM-PBSA analysis revealed that the binding free energy estimates for diosgenin and monohydroxy spirostanol is comparable to the reference drug, lapatinib. This study provides evidence that diosgenin and monohydroxy spirostanol may have the potential to act as dual suppressors of EGFR and HER2. Additional in vivo and in vitro research are needed to certify these results and assess their efficacy and safety as cancer therapy agents. The experimental data reported and these results are in agreement.

Phytochemical composition and bioactivities of Crataegus aronia as antioxidant, antibacterial and antioxidative stress in red blood cells - Is it a window of hope for children with glucose-6-phosphate dehydrogenase deficiency.

Background: Crataegus aronia (C. aronia) extracts have been used medicinally since ancient times and are often utilized in traditional Arab medicine. An extensive study has revealed that Crataegus species have antioxidant, antibacterial, anti-inflammatory, and hypotensive properties. Objectives: This work was performed to explore the phytochemical contents of C. aronia extract, as well as its antioxidant and antibacterial properties, and to assess the lipid peroxidation level as an oxidative stress biomarker in erythrocytes. Methods: Chemical constituents in the methanolic extract of C. aronia were identified by gas chromatography-mass spectrometry and their relative concentrations were determined. The antioxidant activity of C. aronia extract was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The effect of C. aronia on the concentration of malondialdehyde (MDA) in the erythrocyte hemolysates was studied. Also, the crude extract was assessed for its antimicrobial activity through agar diffusion and microbroth dilution assays. Key findings: The DPPH IC50 value of the extract showed that the antioxidants activity was equal to (14.3 µg/mL) and according to FRAP assay, the antioxidant activity was in the range of 33.9 µmol-82.86 µmol Fe+2/g dw. The extract exerts a protective effect against oxidative stress in RBCs and shows a 50% inhibition of malonyldialdehyde (MDA) at 39.48 µg/mL extract. Minimum inhibitory concentrations were found in the range of 800-1000 µg/mL of leave extracts. The phytochemical analysis showed that the total phenols, flavonoids, and flavonols content were 494.071 mg GAE/g extract, 155.251 mg RE/g extract, and 103.2049 mg RE/g extract). C. aronia extract contains alkaloids, flavonoids, terpenoids, and steroids. Crude extract of C. aronia was more potent in inhibiting the growth of B. subtilis, S. aureus and M. luteus with MIC and MBC values of 800,800 and 1000 µg/mL, respectively. According to GC-MS, 20 compounds were identified: dihydro-3-methylene-5-methyl-2-furanone (14.71%), hexanoic acid (6.57%), ethyl 3,5-ditert-butyl-4-hydroxybenzoate (6.4%), N, N-dimethylheptadecan-1-amine (4.91%), methyl 2-oxobutanoate (4.14%), glyceraldehyde (3.98%), and 2-methoxy-1-(2-nitroethenyl)-3-phenylmethoxybenzene (3.16%), were the major constituents. Conclusion: This study may open a window of hope for children with Glucose-6-phosphate dehydrogenase disorder by possible utilization of the active ingredients of C. aronia to minimize both oxidative stress and infection which negatively impact the disease sequelae.According to these in vitro experiments, this plant extract has a significant amount of natural antioxidants, which may aid in the protection of various oxidative stresses. As a result, employing the active components of C. aronia to minimize oxidative stress and infection, both of which have a detrimental impact on disease sequelae, may bring hope to children with Glucose-6-phosphate dehydrogenase disorder.

Assessment of antioxidant, antimicrobial, and anticancer activities of Sisymbrium officinale plant extract.

The most efficient and safe source of medications is the natural and traditional medications which are produced from plants and herbs. In this study, Sisymbrium officinale (S. officinale) was tested to explore its total phenolic and flavonoids contents. Antioxidant, antimicrobial, and anticancer activities were assessed as well. S. officinale was bought from a local Palestinian market, air-dried, and extracted with 99% ethanol with the aid of ultrasonication. The extract was tested on three types of bacteria using well diffusion method. The anti-microbial testing included three different types of bacteria, two gram-positive bacteria, Streptococcus and Staphylococcus and E. coli as a gram-negative bacterium. Antioxidant activity of the plant extract was conducted using DPPH method, while total phenolic and flavonoids contents were performed using a well-known assay chemical method. Anticancer activity of the extract was conducted against two cancer cell lines (breast (MCF7) and colon (HCT116) cancer cell lines). Results showed that the extract is rich polyphenolic and flavonoids and has strong antioxidant activity reflected by inhibition of free radicals (DPPH) (193.7 ± 3.4). The plant extract showed also strong antimicrobial activity against both E. coli and Streptococcus bacteria with of inhibition of 10 and 14 mm respectively. The extract of this plant also showed anticancer activity (about 6%) against MCF7 (breast cancer cell line).

Production of medium-sized chitosan oligomers using molecular sieves and their antibacterial activity.

Chitosan, derived from the natural polysaccharide chitin, was fragmented in very dilute acetic acid solutions using zeolites and molecular sieves, a type of zeolites, under variable reaction conditions of temperature, acid concentration, duration of reaction, and zeolites of variable pore sizes. Fragmentation resulted in the formation of appreciable amounts of chitosan oligomers comprised of 4-8 units, which were studied by using LC-MS, MS, as well as IR spectroscopy. The prepared fragments were tested for their biological activity and some of them showed antibacterial activity against Gram-positive bacteria.

Thiacrown Ethers Engaged C60 through Charge Transfer: Experimental and Theoretical Study.

UV-Vis spectroscopy is used to study the charge transfer complexes of thiacrown ethers 1-6 with fullerene. The size of TCE1-6 and the nature of the heteroatoms (N, O and S) have been systematically changed to examine the effect of these factors on the HOMO/LUMO energy levels, the optical energy gap and the interactions between TCE's and C60. The negative and positive values of ΔS designate the structural forming method and the randomness of the free solvent molecules, respectively. Thermodynamics and stability data show that the complexes have a 1:1 ratio that has been emphasized by density functional theory calculations. Additionally, they show a synergetic interplay of donor-acceptor, π-π, and n-π interactions, which are the basis for the affinity of our novel receptors toward C60. The proposed system of enzyme model suggests a development concept in the future design of enzyme model organic photovoltaic systems.

Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15.

Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.

Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay.

In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay. These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line. Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect. We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase. The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site.