New N-Alkylated Heterocyclic Compounds as Prospective NDM1 Inhibitors: Investigation of In Vitro and In Silico Properties.

A new family of pyrazole-based compounds (1-15) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, 1H, 13C NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli, S. aureus, C. freundii, and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.

Synthesis, characterization, reaction mechanism prediction and biological study of mono, bis and tetrakis pyrazole derivatives against Fusarium oxysporum f. sp. Albedinis with conceptual DFT and ligand-protein docking studies.

Twelve heterocyclic compounds were prepared using the condensation of hydroxymethanol pyrazole derivatives with different primary aminesas example 2-aminothiazole and 1-aminobenzotriazole to have a diverse productin good yield up to 97%. Those ligands were tested against Fusarium oxysporum f. sp. Albedinis fungi (BAYOUD Disease) with IC50 = 25.6-33.2 µg/ml. After experiments, theoretical investigations were done as DFT study to know the ligands molecular reactivity and the-ligandprotein- docking study to know the possible binding between the prepared ligands with two biological targets: FGB1 (Fusarium oxysporum Guanine nucleotide-binding protein beta subunitprimary amino acid sequence) and Fophy (Fusarium oxysporum phytase domain enzyme). Of all the obtained results, the experimental ones were well correlated with the theoretical with the most common thing between those compounds is (Nδ--Nδ+) which is the antifungal pharmacophore as proposed pincers for Foa inhibition. From docking studies over FGB1 and Fophy, the ligand 9 has the best binding energy of -6.4872 kcal/mol in FGB1 active site and -5.5282 kcal/mol in Fophy active site, but better correlation with Fophy than FGB1 which is followed by PLIF graph to get that Arg116, Arg120 and Lys336 are the vital amino acids of fophy protein based the study over the chosen active site.

New Heterocyclic Compounds: Synthesis, Antioxidant Activity and Computational Insights of Nano-Antioxidant as Ascorbate Peroxidase Inhibitor by Various Cyclodextrins as Drug Delivery Systems.

AIM: The synthesis of seven new antioxidant agents based on the combination of thiazole, pyridine, triazole and pyrazole moieties. The studies of their antioxidant activity using DPPH reduction method. The DFT analysis of the 7 ligands. The docking study was also investigated. The better binding affinity with α-cyclodextrin as best drug delivery system. BACKGROUND: The screening of new antioxidant compounds and find the good mechanism for binding sites, with correlating between experience and computer theory. OBJECTIVES: The DFT analysis of the 7 synthesized ligands.The docking study was also investigated by using the amino acids Ala167 and Arg172. The better binding affinity with α-cyclodextrin as best drug delivery system. METHODS: The studies of their antioxidant activity using DPPH reduction method. RESULTS: Chemistry: synthesis of 7 ligands by condensation reaction with 89% yield. Antioxidant activities using DPPH reduction with a good value IC50=13.05 ± 3.73 µg/ml. Using DFT (EHOMO and ELUMO) and Docking APX with the amino acids Ala167 and Arg172 compared to the ascorbic acid. Correlation between all these properties. α-cyclodextrin as best drug delivery system (better binding affinity than caffeic acid). CONCLUSION: For the drug delivery study, The ACD is best system for all the compounds due to the smallest cavity size which makes the binding affinities favorable and possible to prepare prospective nano-antioxidants.

Mono-Alkylated Ligands Based on Pyrazole and Triazole Derivatives Tested Against Fusarium oxysporum f. sp. albedinis: Synthesis, Characterization, DFT, and Phytase Binding Site Identification Using Blind Docking/Virtual Screening for Potent Fophy Inhibitors.

Twelve recent compounds, incorporating several heterocyclic moieties such as pyrazole, thiazole, triazole, and benzotriazole, made in excellent yield up to 37-99.6%. They were tested against Fusarium oxysporum f. sp. albedinis fungi (Bayoud disease), where the best results are for compounds 2, 4, and 5 with IC50 = 18.8-54.4 µg/mL. Density functional theory (DFT) study presented their molecular reactivity, while the docking simulations to describe the synergies between the trained compounds of dataset containing all the tested compounds (57 molecules) and F. oxysporum phytase domain (Fophy) enzyme as biological target. By comparing the results of the docking studies for the Fophy protein, it is found that compound 5 has the best affinity followed by compounds 2 and 4, so there is good agreement with the experimental results where their IC50 values are in the following order: 74.28 (5) < 150 (2) < 214.10 (4), using Blind docking/virtual screening of the homology modeled protein and two different tools as Autodock Vina and Dockthor web tool that gave us predicted sites for further antifungal drug design.

New thiazole, pyridine and pyrazole derivatives as antioxidant candidates: synthesis, DFT calculations and molecular docking study.

Novel heterocyclic compounds containing pyrazole, thiazole and pyridine moieties were designed and prepared based on the condensation reaction between 1,3-thiazole or aminopyridine derivatives and 1H-pyrazole,3,5-dimethyl-1H-pyrazole or 1,2,4-triazole. Their structures were confirmed with FTIR, 1H and 13C NMR analyses. DPPH scavenging assay was used to evaluate their antioxidant potential. The ligand 4 showed the best antioxidant activity with an IC50 = 4.67 µg/mL, while IC50 values of the other compounds were found to be ranging from 20.56 to 45.32 µg/mL. DFT and molecular docking studies were performed in order to gain better insights and to understand the relationship between the structures of the studied compounds and their antioxidant activities. The results obtained revealed a good agreement between the experimental and the theoretical findings.

New synthesis of two tridentate bipyrazolic compounds and their cytotoxic activity tumor cell lines.

Two new tripodal compounds - 4-{bis[(3,5-dimethyl-1H-pyrazole-1-yl)methyl]amino}butane-1-ol (1); ethyl 1-[((2-hydroxyethyl){[3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl]methyl} amino)methyl]-5-methyl-1H-pyrazole-3-carboxylate (2) were reported. The evaluation of the cytotoxic properties in vitro of these ligands, was examined on two tumor cell lines - P815 (mastocytome murine) and Hep (carcinoma of human larynx). The concentration required to induce 50% of lysis (IC(50)) was more pronounced against P815 cell line (IC(50): 39.42 microg mL(-1) for the compound 1 and 97.74 microg mL(-1) for the compound 2) than the Hep cell line (IC(50): 83.49 microg mL(-1) for compound 1 and 185.30 microg mL(-1) for compound 2). Statistical analysis shows that the compound 1 is two to three folds more cytotoxic than the compound 2 (p < 0.05). Interestingly, the cytotoxic activity depends strongly on both the substituents linked to the aminic nitrogen and pyrazolic rings.

4-[Bis(1,5-dimethyl-1H-pyrazol-3-yl-methyl)amino]phenol monohydrate.

The crystal structure of the title compound, C18H23N5O.H2O, shows molecules containing a phenol group linked perpendicularly to a roughly planar fragment comprising two pyrazole rings. Molecules are stacked perpendicular to the [101] direction, with their phenol groups disposed alternately. The molecular packing in the crystal is stabilized by hydrogen bonding involving water molecules.