Phytochemical Composition, In Vitro Antimicrobial, Antioxidant, and Enzyme Inhibition Activities, and In Silico Molecular Docking and Dynamics Simulations of Centaurea lycaonica: A Computational and Experimental Approach.

Centaurea lycaonica is a local endemic species from the Centaurea L. genus. The Centaurea species has a wide range of usage in treating diseases in folk medicine. There are limited biological activity studies on this species in the literature. This study investigated enzyme inhibition and antimicrobial activity, antioxidant effect, and chemical content of extract and fractions of C. lycaonica. Enzyme inhibition activity was tested by α-amylase, α-glucosidase, and tyrosinase enzyme inhibition methods and antimicrobial activity by the microdilution method. The antioxidant activity was investigated using DPPH•, ABTS•+, and FRAP tests. The chemical content was determined by LC-MS/MS. The methanol extract showed the highest activity for α-glucosidase and α-amylase, even surpassing the positive control acarbose, with IC50 values of 56.333 ± 0.986 and 172.800 ± 0.816 µg/mL, respectively. Additionally, the ethyl acetate fraction also exhibited high activity for α-amylase with an IC50 value of 204.067 ± 1.739 µg/mL and tyrosinase with an IC50 value of 213.900 ± 1.553 µg/mL. Moreover, this extract and fraction were found to have the highest total phenolic and flavonoid contents and antioxidant activity. Additionally, LC-MS/MS analyses of active extract and fraction revealed mainly the presence of phenolic compounds and flavonoids. In silico molecular docking and molecular dynamics simulation studies of determining compounds apigenin and myristoleic acid, common in CLM and CLE extracts and active against α-glucosidase and α-amylase, were performed. In conclusion, methanol extract and ethyl acetate fraction showed potential enzyme inhibition and antioxidant activity as a natural agent. Molecular modeling studies corroborate the findings of in vitro activity analyses.

Investigation of Antimicrobial Activity of Some Ethylparaben Hydrazide-Hydrazone Derivatives.

Objectives: The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules. Materials and Methods: In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. Results: The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 µg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 µg/mL against Staphylococcus aureus strain (ATCC 29213). Conclusion: Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.

Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents.

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 µg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f.

Assessment of Phenolic Composition, Antioxidant Potential, Antimicrobial Properties, and Antidiabetic Activity in Extracts Obtained from Schinus molle L. Leaves and Fruits.

BACKGROUND: The current research centers on exploring the antioxidant, antimicrobial, and antidiabetic features of Schinus molle L. grown in Turkey. METHODS: Quantitative analysis of chlorogenic acid, caffeic acid, and hyperoside levels in leaf, ripe fruit, and raw fruit extracts was conducted using High-Performance Liquid Chromatography (HPLC) in a 70% methanol-water mixture. Among the extracts, the methanol extract from ripe fruits displayed the highest chlorogenic acid concentration, measuring at 2.040% ± 0.172% standard deviation (SD). Moreover, analysis of their total phenolic and flavonoid contents was carried out. Antioxidant power was assessed through different chemical assays, together with their antimicrobial and anti-diabetic properties. RESULTS: The results of DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and reducing power assays showed that leaf and ripe fruit alcoholic extract exhibited peak performance. While the MIC ( minimum inhibitory concentration) values of the extracts were determined to have moderate bactericidal effects on Staphylococcus aureus, Escherichia coli, and Candida albicans it was observed that none of the extracts displayed biofilm inhibition. The inhibition percentage of α-glucosidase enzyme activity for the methanol extract of raw fruits was determined to be 99.11 ± 1.61. In diabetic ß-TC cells, glucose level was measured as 129 ± 2.03 mg/dL, and insulin amount was measured as 37.2 ± 0.02 mg/dL. CONCLUSIONS: The findings of our study seem to have important implications for future research, as Schinus molle L. may be a potential pharmaceutical candidate with important pharmacological activities.

Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of New Thiosemicarbazide-Triazole Hybrid Derivatives of (S)-Naproxen.

The discovery of new antimicrobial molecules is crucial for combating drug-resistant bacterial and fungal infections that pose a dangerous threat to human health. In the current research, we applied a molecular hybridization approach to synthesize original thiosemicarbazide-triazole derivatives starting from (S)-naproxen (7a-7k). After structural characterization using FT-IR, 1 H-NMR, 13 C-NMR, and HR-MS, the obtained compounds were screened for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Candida albicans ATCC 10231 and their isolates, as well. Although all compounds were found to be moderate antimicrobial agents, in general, their antibacterial activities were better than antifungal effects. Among the tested compounds, 7j carrying nitrophenyl group on the thiosemicarbazide functionality represented the best MIC value against S. aureus isolate. Finally, molecular docking studies were performed in the active pocket of S. aureus flavohemoglobin to rationalize the obtained biological data.

Quantum mechanical, virtual screening, molecular docking, molecular dynamics, ADME and antimicrobial activity studies of some new indole-hydrazone derivatives as potent agents against E. faecalis.

In this study, a new series of indole-5-carbaldehyde hydrazone derivative compounds were designed, synthesized, and their antimicrobial activities were determined by the microdilution method, and the in vitro cytotoxic effects on Beas-2b cell lines were investigated by MTT assay. When the activity results were examined, 5i12 showed promising activity against E. faecalis with MIC: 2 µg/mL compared to ampicillin, gentamicin, and vancomycin, although the antimicrobial activities of the indole derivatives were generally weaker than those of the standard drugs. Compounds showed no cytotoxic activity on the A549, MCF-7, and Beas-2b cell lines. Molecular docking studies were performed on 15 different proteins to understand the mechanism of 5i12's good antimicrobial action against E. faecalis, and it was concluded that the compounds interacted with FabH, not enough other protein structures. Molecular dynamics simulations were performed to investigate the protein-ligand stability of the most active compound against E. faecalis. The RMSD value of 5i12 varied between 0.02 and 0.16 nm during the MD simulation. The apoprotein peaked at 0.55 nm at the beginning of the simulation and stabilized below 0.5 nm. The theoretical ADME profiles of all compounds were calculated and found to comply with Lipinski and other limiting rules. In addition, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis for 5i12 were calculated using the 6-311 G (d,p) base set and DFT/B3LYP theory, and the results were visualized. Communicated by Ramaswamy H. Sarma.