Synthesis, Crystal Structures, Genotoxicity, and Antifungal and Antibacterial Studies of Ni(II) and Cd(II) Pyrazole Amide Coordination Complexes.

In this study, we synthesized two coordination complexes based on pyrazole-based ligands, namely 1,5-dimethyl-N-phenyl-1H-pyrazole-3-carboxamide (L1) and 1,5-dimethyl-N-propyl-1H-pyrazole-3-carboxamide (L2), with the aim to investigate bio-inorganic properties. Their crystal structures revealed a mononuclear complex [Ni(L1)2](ClO4)2 (C1) and a dinuclear complex [Cd2(L2)2]Cl4 (C2). Very competitive antifungal and anti-Fusarium activities were found compared to the reference standard cycloheximide. Additionally, L1 and L2 present very weak genotoxicity in contrast to the observed increase in genotoxicity for the coordination complexes C1 and C2.

Coordination Complexes Built from a Ditopic Triazole-Pyrazole Ligand with Antibacterial and Antifungal Performances.

Four mononuclear complexes (H3O){[NiL3](ClO4)3} (1), [CoL3](ClO4)2·2H2O (2), [CdL2Cl2] (3) and [CuL3](NO3)2 (4) have been prepared employing a newly synthesized 1,2,4-triazole ligand: 3-(3,5-dimethyl-1H-pyrazol-1-yl)-1H-1,2,4-triazole (L). The structures of the complexes, which crystallized in P63/m (1), P-1 (2), P1 (3), and P21/c (4), are reviewed within the context of the cooperative effect of the hydrogen bonding network and counter anions on the supramolecular formations. Moreover, within the framework of biological activity examination, these compounds showed favorable antibacterial performances compared to those of various species of bacteria, including both Gram-positive and Gram-negative strains. Significant antifungal inhibitory activity towards Fusarium oxysporum f. sp. albedinis fungi was recorded for 3 and 4 over the ligand L.

Crocus sativus L. Stigmas, Tepals, and Leaves Ameliorate Gentamicin-Induced Renal Toxicity: A Biochemical and Histopathological Study.

The most costly spice in the world, Crocus sativus L. (C. sativus), has been used for more than 3,000 years. It has various beneficial applications in a range of fields, including aromas, colorants, and medications, but its usefulness as a food flavoring and coloring ingredient is the highest. Large quantities of by-products from the processing of saffron are typically thrown as unwanted bio-residues. This study's goal was to assess and compare the nephroprotective effects of hydroethanolic extracts of C. sativus stigmas, tepals, and leaves on gentamicin (GM)-induced nephrotoxicity in rats. For that, we used a biochemical and histological investigation to propose new pharmaceutical valorizations. Based on the biochemical and histological analyses, it is concluded that all the studied parts of C sativus showed a renoprotective effect. Markedly, tepals revealed the most significant reduction of relative liver weight (p < 0.05), water intake (p < 0.05), plasma creatinine (p < 0.01), plasma urea (p < 0.01), plasma uric acid (p < 0.05), urinary protein (p < 0.01) and albumin (p < 0.001), and renal malondialdehyde (MDA) (p < 0.001). In addition, C. sativus tepals caused a significant increase in body weight (p < 0.05), urinary creatinine (p < 0.01), creatinine clearance (p < 0.05), and urinary urea (p < 0.05) compared with the gentamicin untreated (GM) group. This is confirmed by the histopathological study which shows that treatment with stigmas, tepals, and leaves preserved kidney morphology at the glomerular and tubular cell level. The studied extracts exhibit good recovery potential for nephrotoxicity induced by gentamicin. In order to create potent dietary supplements or phytomedicines, it would also be very interesting to confirm these actions through clinical research.

Novel family of bis-pyrazole coordination complexes as potent antibacterial and antifungal agents.

A new pyrazole ligand, N,N-bis(2(1',5,5'-trimethyl-1H,1'H-[3,3'-bipyrazol]-1-yl)ethyl)propan-1-amine (L) was synthesized and characterized by 1H-NMR, 13C-NMR, FT-IR and HRMS. The coordination ability of the ligand has been employed for the construction of a new family of coordination complexes, namely: [Cu2LCl4] (1), [ML(CH3OH)(H2O)](ClO4)2 (MII = Ni (2), Co (3)) and [FeL(NCS)2] (4). The series of complexes were characterized using single-crystal X-ray diffraction, HRMS, FT-IR and UV-visible spectroscopy. Moreover, the iron(ii) analogue was investigated by 57Fe Mössbauer spectroscopy and SQUID magnetometry. Single-crystal X-ray structures of the prepared complexes are debated within the framework of the cooperative effect of the hydrogen bonding network and counter anions on the supramolecular formations observed. Furthermore, within the context of biological activity surveys, these compounds were reviewed against different types of bacteria to validate their efficiency, including both Gram-positive as well as Gram-negative bacteria. Enhanced behaviour towards Fusarium oxysporum f. sp. albedinis fungi, were detected for 1 and 4.

Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves.

The present study investigated the antioxidant activity, metal chelating ability and genoprotective effect of the hydroethanolic extracts of Crocus sativus stigmas (STG), tepals (TPL) and leaves (LV). We evaluated the antioxidant and metal (Fe2+ and Cu2+) chelating activities of the stigmas, tepals and leaves of C. sativus. Similarly, we examined the genotoxic and DNA protective effect of these parts on rat leukocytes by comet assay. The results showed that TPL contains the best polyphenol content (64.66 µg GA eq/mg extract). The highest radical scavenging activity is shown by the TPL (DPPH radical scavenging activity: IC50 = 80.73 µg/mL). The same extracts gave a better ferric reducing power at a dose of 50 µg/mL, and better protective activity against ß-carotene degradation (39.31% of oxidized ß-carotene at a 100 µg/mL dose). In addition, they showed a good chelating ability of Fe2+ (48.7% at a 500 µg/mL dose) and Cu2+ (85.02% at a dose of 500 µg/mL). Thus, the antioxidant activity and metal chelating ability in the C. sativus plant is important, and it varies according to the part and dose used. In addition, pretreatment with STG, TPL and LV significantly (p < 0.001) protected rat leukocytes against the elevation of percent DNA in the tail, tail length and tail moment in streptozotocin- and alloxan-induced DNA damage. These results suggest that C. sativus by-products contain natural antioxidant, metal chelating and DNA protective compounds, which are capable of reducing the risk of cancer and other diseases associated with daily exposure to genotoxic xenobiotics.

An Insight into All Tested Small Molecules against Fusarium oxysporum f. sp. Albedinis: A Comparative Review

Bayoud disease affects date palms in North Africa and the Middle East, and many researchers have used various methods to fight it. One of those methods is the chemical use of synthetic compounds, which raises questions centred around the compounds and common features used to prepare targeted molecules. In this review, 100 compounds of tested small molecules, collected from 2002 to 2022 in Web of Sciences, were divided into ten different classes against the main cause of Bayoud disease pathogen Fusarium oxysporum f. sp. albedinis (F.o.a.) with structure-activity relationship (SAR) interpretations for pharmacophore site predictions as (δ-···Î´-), where 12 compounds are the most efficient (one compound from each group). The compounds, i.e., (Z)-1-(1.5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy but-2-en-1-one 7, (Z)-3-(phenyl)-1-(1,5-dimethyl-1H-pyrazole-3-yl)-3-hydroxyprop-2-en-1-one 23, (Z)-1-(1,5-Dimethyl-1H-pyrazole-3-yl)-3-hydroxy-3-(pyridine-2-yl)prop-2-en-1-one 29, and 2,3-bis-[(2-hydroxy-2-phenyl)ethenyl]-6-nitro-quinoxaline 61, have antifungal pharmacophore sites (δ-···Î´-) in common in N1---O4, whereas other compounds have only one δ- pharmacophore site pushed by the donor effect of the substituents on the phenyl rings. This specificity interferes in the biological activity against F.o.a. Further understanding of mechanistic drug-target interactions on this subject is currently underway.

The Major Stilbene Compound Accumulated in the Roots of a Resistant Variety of Phoenix dactylifera L. Activates Proteasome for a Path in Anti-Aging Strategy.

The main objective of the present study is to estimate, through differential analysis, various biological activities of total phenolics content in alcoholic extracts of three date palm varieties sensitive or resistant to Fusarium oxysporum. sp Albidinis. Here, stilbene products with antioxidant and bioactive capacities were evidenced in resistant variety Taabdount (TAAR). Furthermore, the methanolic fraction of the TAAR-resistant date palm variety contains a significant product, determined by LC-MS/MS and 1H, 13C NMR, belonging to the family of hydroxystilbenes, which exhibits antioxidant capacities, inhibits the mushroom tyrosinase activity, and activates and exerts a protective effect on hypochlorite-induced damage in 20S proteasome of human dermal fibroblast aged cells. Altogether, the present results indicate that hydroxystilbene present in resistant Phoenix dactylifera L. should be studied to understand the way that the stilbene could exert anti-aging ability.

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.

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.

Synthesis, Biochemical Characterization, and Theoretical Studies of Novel ß-Keto-enol Pyridine and Furan Derivatives as Potent Antifungal Agents.

In the present study, we report the design and synthesis of new derivatives of the ß-keto-enol grafted on pyridine and furan moieties (L 1 -L 11 ). Structures of compounds were fully confirmed by Fourier transform infrared spectroscopy (FT-IR), 1H NMR, 13C NMR, electrospray ionization/liquid chromatography-mass spectrometry (ESI/LC-MS), and elemental analysis. The compounds were screened for antifungal and antibacterial activities (Escherichia coli, Bacillus subtilis, and Micrococcus luteus). In vitro evaluation showed significant fungicidal activity for L 1 , L 4 , and L 5 against fungal strains (Fusarium oxysporum f.sp albedinis) compared to the reference standard. Especially, the exceptional activity has been demonstrated for L 1 with IC50 = 12.83 µg/mL. This compound and the reference benomyl molecule also showed a correlation between experimental antifungal activity and theoretical predictions by Petra/Osiris/Molinspiration (POM) calculations and molecular coupling against the Fgb1 protein. The highest inhibition of bacterial growth for L 1 is due to its strongest binding to the target protein. This report may stimulate the further synthesis of examples of this substance class for the development of new drugs.

Novel ß-keto-enol Pyrazolic Compounds as Potent Antifungal Agents. Design, Synthesis, Crystal Structure, DFT, Homology Modeling, and Docking Studies.

A new family of promising inhibitors bearing ß-keto-enol functionality with greatly improved pharmacophore properties has been prepared. Herein, a series of novel derivatives of ß-keto-enol group embedded with pyrazolic moiety has been designed and synthesized via a one-step procedure using mixed Claisen condensation in the attempt to develop potential antifungal agents. The structures of the synthesized compounds were confirmed by elemental analysis, FT-IR, ESI/LC-MS, and 1H and 13C NMR. In addition, X-ray diffraction analysis (XRD) was used to determine the single crystal structure of compound 10. All of the new compounds have been evaluated for their in vitro antifungal and antibacterial activities. Interestingly, the results indicate that most of the compounds display notable antifungal activity close to that of the benomyl fungicide taken as the standard drug. For the most active compound and for benomyl, a correlation has been evidenced between the experimental antifungal activity and the theoretical predictions by DFT calculations and molecular docking against Fgb1 protein.

Synthesis, crystal structure, DFT studies and biological activity of (Z)-3-(3-bromophenyl)-1-(1,5-dimethyl-1H-pyrazol-3-yl)-3-hydroxyprop-2-en-1-one.

BACKGROUND: Nowadays, is emerging a new generation of highly promising inhibitors bearing the ß-ketoenol functionality. The present work relates to the first synthesis, the structure determination, the DFT studies and the use of a new biomolecule designed with a ß-ketoenol group bounded to a pyrazolic moiety. RESULT: A novel ß-ketoenol-pyrazole has been synthesized, well characterized and its structure was confirmed by single crystal X-ray diffraction. The electron densities and the HOMO-LUMO gap have been calculated using the DFT method with BLYP, PW91, PWC functionals and 6-31G* basis set. An evaluation of the molecule stability is provided by a NBO analysis and the calculated Fukui and Parr functions have been used to locate the reactive electrophile and nucleophile centers in the molecule. The synthesized compound, screened for its in vitro antifungal behavior against the Fusarium oxysporum f.sp. albedinis FAO fungal strains, shows a moderate activity with an inhibition percentage of 46%. The product was also tested against three bacterial strains (Escherichia coli, Bacillus subtilis and Micrococcus luteus), but no significant effect was observed against these organisms. CONCLUSIONS: Density functional calculations are used to evaluate the HOMO-LUMO energy gap, the molecular electrostatic potential and to provide a natural bond orbital analysis. The measured antimicrobial activities encourage us to continue searching for other structures, likely to be good antifungal candidates.

Synthesis of Novel ß-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents.

Recently, a new generation of highly promising inhibitors bearing ß-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the ß-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, ¹H-NMR, (13)C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055-0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls.