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Molecules (Basel, Switzerland) Dec 2023Among well-studied and actively developing compounds are polyoxometalates (POMs), which show application in many fields. Extending this class of compounds, we introduce...
Among well-studied and actively developing compounds are polyoxometalates (POMs), which show application in many fields. Extending this class of compounds, we introduce a new subclass of polyoxometal clusters (POMCs) [MoO(μ-L)] (L = pyrazolate (pz) or triazolate (1,2,3-trz or 1,2,4-trz)), structurally similar to POM, but containing binuclear MoO clusters linked by bridging oxo- and organic ligands. The complexes obtained by ampoule synthesis from the binuclear cluster [MoO(CO)(HO)] in a melt of an organic ligand are soluble and stable in aqueous solutions. In addition to the detailed characterization in solid state and in aqueous solution, the biological properties of the compounds on normal and cancer cells were investigated, and antiviral activity against influenza A virus (subtype H5N1) was demonstrated.
Topics: Water; Models, Molecular; Molybdenum; Influenza A Virus, H5N1 Subtype; Triazoles; Pyrazoles; Antiviral Agents
PubMed: 38138569
DOI: 10.3390/molecules28248079 -
Bioorganic & Medicinal Chemistry Letters Sep 2017A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1...
A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K=0.1nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360.
Topics: Dose-Response Relationship, Drug; Humans; Mesylates; Models, Molecular; Molecular Structure; Phenylpropionates; Pyrazoles; Structure-Activity Relationship; TRPV Cation Channels
PubMed: 28838698
DOI: 10.1016/j.bmcl.2017.08.020 -
Scientific Reports Jul 2022Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to...
Design, synthesis, in vitro biological assessment and molecular modeling insights for novel 3-(naphthalen-1-yl)-4,5-dihydropyrazoles as anticancer agents with potential EGFR inhibitory activity.
Currently, the humanity is in a fierce battle against various health-related challenges especially those associated with human malignancies. This created the urge to develop potent and selective inhibitors for tumor cells through targeting specific oncogenic proteins possessing crucial roles in cancer progression and survive. In this respect, new series of pyrazole-thiazol-4-one hybrids (9a-p) were synthesized as potential anticancer agents. All the synthesized molecules exhibited potent antiproliferative actions against breast cancer (BC) T-47D and MDA-MB-231 cell lines with IC ranges 3.14-4.92 and 0.62-58.01, respectively. Moreover, the most potent anti-proliferative counterparts 9g and 9k were assessed against EGFR. They displayed nanomolar inhibitory activity, IC 267 ± 12 and 395 ± 17 nM, respectively. Worth noting, both compounds 9g and 9k induced apoptosis in MDA-MB-231 cells, and resulted in a cell cycle arrest at G2/M phase. Furthermore, an in silico analysis including docking and molecular dynamic simulations was performed.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Design; Drug Screening Assays, Antitumor; ErbB Receptors; Humans; Molecular Docking Simulation; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 35896557
DOI: 10.1038/s41598-022-15050-8 -
Molecules (Basel, Switzerland) Sep 2019Three series of novel thienopyrimidine derivatives -, -, and - were designed and synthesized, and their IC values against four cancer cell lines HepG-2, A549, PC-3, and...
Three series of novel thienopyrimidine derivatives -, -, and - were designed and synthesized, and their IC values against four cancer cell lines HepG-2, A549, PC-3, and MCF-7 were evaluated. Most compounds show moderate cytotoxicity against the tested cancer cell lines. The most promising compound showed moderate activity with IC values of 12.32 ± 0.96, 11.30 ± 1.19, 14.69 ± 1.32, and 9.80 ± 0.93 µM, respectively. The inhibitory activities of compounds and against PI3Kα and mTOR kinase were further evaluated. Compound exhibited PI3Kα kinase inhibitory activity with IC of 9.47 ± 0.63 µM. In addition, docking studies of compounds and were also investigated.
Topics: A549 Cells; Cell Line, Tumor; Class I Phosphatidylinositol 3-Kinases; Drug Design; Hep G2 Cells; Humans; MCF-7 Cells; Molecular Structure; PC-3 Cells; Pyrazoles; Pyrimidines; Structure-Activity Relationship
PubMed: 31547116
DOI: 10.3390/molecules24193422 -
Molecules (Basel, Switzerland) Mar 2019A new series of pyrazole ⁻ and pyrazolo[1,5-]pyrimidine ⁻ were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and...
A new series of pyrazole ⁻ and pyrazolo[1,5-]pyrimidine ⁻ were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-]pyrimidine were synthesized by the conventional method and also subjected to microwave irradiation and under ultrasound conditions. The biological results revealed that most of the tested compounds proved to be active as antibacterial and antifungal agents. The antitumor activity of the synthesized compounds was evaluated against human cancer cell lines, MCF-7, HCT-116, and HepG-2, as compared with Doxorubicin as a control.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Cell Line, Tumor; Doxorubicin; HCT116 Cells; Hep G2 Cells; Humans; MCF-7 Cells; Microbial Sensitivity Tests; Microwaves; Pyrazoles; Pyrimidines
PubMed: 30893820
DOI: 10.3390/molecules24061080 -
Molecules (Basel, Switzerland) Jul 2022In silico evaluation of various regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1-pyrazole-4-carboxylates and their acyclic precursors yielded promising results...
In silico evaluation of various regioisomeric 5- and 3-hydroxy-substituted alkyl 1-aryl-1-pyrazole-4-carboxylates and their acyclic precursors yielded promising results with respect to their binding in the active site of dihydroorotate dehydrogenase of (DHODH). Consequently, four ethyl 1-aryl-5-hydroxy-1-pyrazole-4-carboxylates and their 3-hydroxy regioisomers were prepared by two-step syntheses via enaminone-type reagents or key intermediates. The synthesis of 5-hydroxy-1-pyrazoles was carried out using the literature protocol comprising acid-catalyzed transamination of diethyl [(dimethylamino)methylene]malonate with arylhydrazines followed by base-catalyzed cyclization of the intermediate hydrazones. For the synthesis of isomeric methyl 1-aryl-3-hydroxy-1-pyrazole-4-carboxylates, a novel two-step synthesis was developed. It comprises acylation of hydrazines with methyl malonyl chloride followed by cyclization of the hydrazines with -butoxy-bis(dimethylamino)methane. Testing the pyrazole derivatives for the inhibition of DHODH showed that 1-(naphthalene-2-yl)-5-hydroxy-1-pyrazole-4-carboxylate and 1-(naphthalene-2-yl)-, 1-(2,4,6-trichlorophenyl)-, and 1-[4-(trifluoromethyl)phenyl]-3-hydroxy-1-pyrazole-4-carboxylates (~30% inhibition) were slightly more potent than a known inhibitor, diethyl α-{[(1-indazol-5-yl)amino]methylidene}malonate (19% inhibition).
Topics: Carboxylic Acids; Dihydroorotate Dehydrogenase; Hydrazines; Malonates; Naphthalenes; Plasmodium falciparum; Pyrazoles
PubMed: 35897941
DOI: 10.3390/molecules27154764 -
European Journal of Pharmacology Nov 2016Inflammatory diseases and pain are among the main problems that significantly influence the lifestyle of millions of people and existing therapies are not always...
Inflammatory diseases and pain are among the main problems that significantly influence the lifestyle of millions of people and existing therapies are not always effective and can cause several adverse effects. In this context, the molecular modifications or synthesis of compounds continue being the best strategies for the identification of new compounds for the treatment of pain and inflammation. The aim of this study was to evaluate the analgesic and anti-inflammatory activities of new analogues of pyrazole compounds containing subunits N-phenyl-1-H-pirazoles and 1,3,4-oxadiazole-2(3H)-thione, LQFM-146, LQFM-147 and LQFM-148. In the acetic acid-induced abdominal writhing test, treatments with LQFM-146, LQFM-147 or LQFM-148 at doses 89, 178 and 356µmol/kg p.o. reduced the abdominal writhing in a dose-dependent manner. In the formalin test, these compounds at dose 178µmol/kg p.o. reduced the licking time only in inflammatory phase of this test, suggesting an antinociceptive effect dependent of the anti-inflammatory effect. The treatment with the three compounds in intermediate dose (178µmol/kg p.o.) reduced the edema at all tested time points in the carrageenan-induced paw edema test and reduced polymorphonuclears cell migration, activity myeloperoxidase and TNF-α levels in the carrageenan-induced pleurisy test. Our date suggest that the new compounds LQFM-146, LQFM-147 and LQFM-148 possess satisfactory anti-inflammatory and antinociceptive effects that involves the reduction of pro-inflammatory cytokines and inhibition of the myeloperoxidase enzyme.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Chemistry Techniques, Synthetic; Drug Design; Edema; Male; Mice; Peroxidase; Pyrazoles; Tumor Necrosis Factor-alpha
PubMed: 27590355
DOI: 10.1016/j.ejphar.2016.08.033 -
Molecules (Basel, Switzerland) May 2024To further extend the structure-activity relationships (SARs) of 5-aminopyrazoles (5APs) and identify novel compounds able to interfere with inflammation, oxidative...
To further extend the structure-activity relationships (SARs) of 5-aminopyrazoles (5APs) and identify novel compounds able to interfere with inflammation, oxidative stress, and tumorigenesis, 5APs have been designed and prepared. Some chemical modifications have been inserted on cathecol function or in aminopyrazole central core; in detail: (i) smaller, bigger, and more lipophilic substituents were introduced in and positions of catechol portion (5APs ); (ii) a methyl group was inserted on C3 of the pyrazole scaffold (5APs ); (iii) a more flexible alkyl chain was inserted on N1 position (5APs ); (iv) the acylhydrazonic linker was moved from position 4 to position 3 of the pyrazole scaffold (5APs ). All new derivatives have been tested for radical scavenging (DPPH assay), anti-aggregating/antioxidant (in human platelets) and cell growth inhibitory activity (MTT assay) properties. In addition, in silico pharmacokinetics, drug-likeness properties, and toxicity have been calculated. 5APs emerged to be promising anti-proliferative agents, able to suppress the growth of specific cancer cell lines. Furthermore, derivatives remarkably inhibited ROS production in platelets and 5APs showed interesting in vitro radical scavenging properties. Overall, the collected results further confirm the pharmaceutical potentials of this class of compounds and support future studies for the development of novel anti-proliferative and antioxidant agents.
Topics: Humans; Pyrazoles; Antineoplastic Agents; Antioxidants; Structure-Activity Relationship; Cell Line, Tumor; Cell Proliferation; Molecular Structure
PubMed: 38792163
DOI: 10.3390/molecules29102298 -
Pest Management Science Apr 2022The Varroa mite (Varroa destructor) is an ectoparasite that can affect the health of honey bees (Apis mellifera) and contributes to the loss of colony productivity. The...
BACKGROUND
The Varroa mite (Varroa destructor) is an ectoparasite that can affect the health of honey bees (Apis mellifera) and contributes to the loss of colony productivity. The limited availability of Varroacides with different modes of action in Canada has resulted in the development of chemical resistance in mite populations. Therefore, an urgent need to evaluate new potential miticides that are safe for bees and exhibit high efficacy against Varroa exists. In this study, the acute contact toxicity of 26 active ingredients (19 chemical classes), already available on the market, was evaluated on V. destructor and A. mellifera under laboratory conditions using an apiarium bioassay. In this assay, groups of Varroa-infested worker bees were exposed to different dilutions of candidate compounds. In semi-field trials, Varroa-infested honey bees were randomly treated with four vetted candidate compounds from the apiarium assay in mini-colonies.
RESULTS
Among tested compounds, fenazaquin (quinazoline class) and fenpyroximate (pyrazole class) had higher mite mortality and lower bee mortality over a 24 h exposure period in apiariums. These two compounds, plus spirotetramat and spirodiclofen, were selected for semi-field evaluation based on the findings of the apiarium bioassay trials and previous laboratory studies. Consistent with the apiarium bioassay, semi-field results showed fenazaquin and fenpyroximate had high efficacy (>80%), reducing Varroa abundance by 80% and 68%, respectively.
CONCLUSION
These findings suggest that fenazaquin would be an effective Varroacide, along with fenpyroximate, which was previously registered for in-hive use as Hivastan. Both compounds have the potential to provide beekeepers with an alternative option for managing Varroa mites in honey bee colonies. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Topics: Animals; Bees; Benzoates; Pyrazoles; Quinazolines; Varroidae
PubMed: 34994089
DOI: 10.1002/ps.6788 -
International Journal of Nanomedicine 2019It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad...
INTRODUCTION
It is well known that the grafted multiwalled carbon nanotubes (MWCNTs) have antibacterial activity and lower cytotoxicity. Moreover, pyrazole derivatives have a broad spectrum of biological activity due to their fertile template for many medicinal drugs. On view of these findings we report herein the hybridization between MWCNTs and some pyrazole derivatives as antibacterial agents.
MATERIALS AND METHODS
Pyrazole and pyrazolone derivatives were grafted onto the surface of carboxylated MWCNTs via the reaction of carboxylated MWCNTs and the diazonium salts of pyrazoles and pyrazolones using mixed acid treatment. The insertion of the pyrazole and pyrazolone moieties was characterized by Fourier transform infrared (FTIR) spectroscopy, energy dispersion spectroscopy, transmission electron microscopy, X-ray diffraction and thermogravimetric (TGA).
RESULTS
The results indicate that pyrazole and pyrazolone moieties successfully attached on carboxylated MWCNTs surface. The neat pyrazole and pyrazolone derivatives and their corresponding carbon nanotubes were tested against , and bacteria, and fungi. The results showed that the grafted carbon nanotubes of pyrazole and pyrazolone derivatives have better antimicrobial activity than the neat pyrazole and pyrazolone derivatives. The molecular docking studies were performed on the most potent antimicrobial compounds to investigate the existence of the interactions between the most active inhibitors and Farnesyl pyrophosphate synthase (FPPS).
CONCLUSION
The surface of the carboxylated MWCNTs was successfully grafted with some pyrazole derivatives. The antibacterial activity was investigated for the newly synthesized compounds and indicated that the grafted MWCNTs have good antibacterial activity toward some pathogenic types of bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Catalytic Domain; Fungi; Ligands; Microbial Sensitivity Tests; Molecular Docking Simulation; Nanotubes, Carbon; Pyrazoles; Spectroscopy, Fourier Transform Infrared; Thermogravimetry; X-Ray Diffraction
PubMed: 31686804
DOI: 10.2147/IJN.S182699