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Molecular Diversity Feb 2011One-pot synthesis of different benzochromeno-pyrazole derivatives has been reported via reaction of aldehydes, 3-methyl-1H-pyrazol-5(4H)-one and α-naphthol/β-naphthol...
One-pot synthesis of different benzochromeno-pyrazole derivatives has been reported via reaction of aldehydes, 3-methyl-1H-pyrazol-5(4H)-one and α-naphthol/β-naphthol in the presence of sulfamic acid.
Topics: Aldehydes; Benzopyrans; Pyrazoles; Sulfonic Acids
PubMed: 20683770
DOI: 10.1007/s11030-010-9263-4 -
Bioorganic & Medicinal Chemistry Letters Jul 2021A series of novel pyrazole-benzimidazole derivatives (6-42) have been designed, synthesized and evaluated for their in vitro antiproliferative activity against the...
A series of novel pyrazole-benzimidazole derivatives (6-42) have been designed, synthesized and evaluated for their in vitro antiproliferative activity against the HCT116, MCF-7 and Huh-7 cell lines. Among them, compounds 17, 26 and 35 showed significant antiproliferative activity against HCT116 cell lines with the IC values of 4.33, 5.15 and 4.84 μM, respectively. Moreover, fluorescent staining studies showed compound 17 could induce cancer cells apoptosis. The flow cytometry assay revealed that compound 17 could induce cell cycle arrest at G0/G1 phase. All in all, these consequences suggest that pyrazole-benzimidazole derivatives could serve as promising compounds for further research to develop novel and highly potent cancer therapy agents.
Topics: Antineoplastic Agents; Benzimidazoles; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 33979690
DOI: 10.1016/j.bmcl.2021.128097 -
Bioorganic & Medicinal Chemistry Jun 2020Myeloperoxidase (MPO) activity and subsequent generation of hypochlorous acid has been associated with the killing of host-invading microorganisms (e.g. bacteria,...
Myeloperoxidase (MPO) activity and subsequent generation of hypochlorous acid has been associated with the killing of host-invading microorganisms (e.g. bacteria, viruses, and fungi). However, during oxidative stress, high MPO activity can damage host tissue and is linked to several chronic inflammatory conditions. Herein, we describe the development of a novel biaryl, indole-pyrazole series of irreversible mechanism-based inhibitors of MPO. Derived from an indole-containing high-throughput screen hit, optimization efforts resulted in potent and selective 6-substituted indoles with good oral bioavailability and in vivo activity.
Topics: Animals; Enzyme Inhibitors; Half-Life; Indoles; Mice; Peritonitis; Peroxidase; Pyrazoles; Structure-Activity Relationship
PubMed: 32503688
DOI: 10.1016/j.bmc.2020.115548 -
Bioorganic & Medicinal Chemistry Letters Aug 2012As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These...
As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These compounds were tested for antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system, antifungal activity against a pathogenic strain of fungi and antibacterial activity against gram-positive and gram-negative organisms. Among them tested, many compounds showed good to excellent antimicrobial and antitubercular activity. The results suggest that hydrazones, 2-azetidinones and 4-thiazolidinones bearing a core pyrazole scaffold would be potent antimicrobial and antitubercular agents.
Topics: Anti-Infective Agents; Antitubercular Agents; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship
PubMed: 22695129
DOI: 10.1016/j.bmcl.2012.05.063 -
Archiv Der Pharmazie May 2021Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are...
Mycobacterium tuberculosis (Mtb) is one of the most dangerous pathogens affecting immunocompetent and immunocompromised patients worldwide. Novel molecules, which are efficient and can reduce the duration of therapy against drug-resistant strains, are an urgent unmet need of the hour. In our current study, a series of new 2-(3-phenyl-1H-pyrazol-1-yl)acetamide and N'-benzylidene-2-(3-phenyl-1H-pyrazol-1-yl)acetohydrazide derivatives were designed, synthesized, and evaluated for their antimycobacterial potential. The biological evaluation revealed that 6b, 6m, 6l, 7a, and 7k exhibited selective and potent inhibitory activity against Mtb. Furthermore, compounds 6m and 7h were found to be nontoxic to Vero cells with CC of greater than 20 and 80 mg/ml, respectively, and exhibited promising selectivity indices (SI) of greater than 666 and 320, respectively. All derivatives exhibited excellent ADME (absorption, distribution, metabolism, and excretion) properties in silico. Also, all the derivatives were found compliant with Lipinski's rule of five, showing their druggability profile. Molecular docking insights of these derivatives have shown outstanding binding energies on the mycobacterial membrane protein large transporters. These results indicate that this scaffold may lead to a potential antimycobacterial drug candidate in the discovery of antitubercular agents.
Topics: Acetamides; Antitubercular Agents; Dose-Response Relationship, Drug; Drug Design; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship
PubMed: 33351199
DOI: 10.1002/ardp.202000349 -
Molecules (Basel, Switzerland) Oct 2016A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in...
A one-pot reaction was described that results in various pyrazole-thiobarbituric acid derivatives as new pharmacophore agents. These new heterocycles were synthesized in high yields with a broad substrate scope under mild reaction conditions in water mediated by NHEt₂. The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques. The new compounds were evaluated for their antibacterial and antifungal activity. Compounds and were the most active compounds against with MIC = 4 µg/L. Compound exhibited the best activity against and with MIC = 16 µg/L. However, compounds and were the most active against with MIC = 16 µg/L. Molecular docking studies for the final compounds and standard drugs were performed using the OpenEye program.
Topics: Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Humans; Microbial Sensitivity Tests; Molecular Docking Simulation; Pyrazoles; Staphylococcus aureus; Thiobarbiturates
PubMed: 27735850
DOI: 10.3390/molecules21101337 -
Molecules (Basel, Switzerland) Sep 2014In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were...
In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank) Donk, Fusarium oxysporum (S-chl) f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27-32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.
Topics: Antifungal Agents; Fungi; Molecular Structure; Pyrazoles; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship
PubMed: 25203055
DOI: 10.3390/molecules190914036 -
Molecules (Basel, Switzerland) May 2019Copper(II) complexes of bis(pyrazol-1-yl)- and bis(triazol-1-yl)-acetate heteroscorpionate ligands have been synthesized. The copper(II) complexes...
Copper(II) complexes of bis(pyrazol-1-yl)- and bis(triazol-1-yl)-acetate heteroscorpionate ligands have been synthesized. The copper(II) complexes [HC(COOH)(pz)]Cu[HC(COO)(pz)]·ClO, [HC(COOH)(pz)]Cu(ClO) (pz = 3,5-dimethylpyrazole; pz = pyrazole) were prepared by the reaction of Cu(ClO)·6HO with bis(3,5-dimethylpyrazol-1-yl)acetic acid (HC(COOH)(pz)) and bis(pyrazol-1-yl)acetic acid (HC(COOH)(pz)) ligands in ethanol solution. The copper(II) complex [HC(COOH)(tz)]Cu(ClO)·CHOH (tz = 1,2,4-triazole) was prepared by the reaction of Cu(ClO)·6HO with bis(1,2,4-triazol-1-yl)acetic acid (HC(COOH)(tz)) ligand in methanol solution. The synthesized Cu(II) complexes, as well as the corresponding uncoordinated ligands, were evaluated for their cytotoxic activity in monolayer and 3D spheroid cancer cell cultures with different Pt(II)-sensitivity. The results showed that [HC(COOH)(pz)]Cu[HC(COO)(pz)]·ClO was active against cancer cell lines derived from solid tumors at low IC and this effect was retained in the spheroid model. Structure and ultra-structure changes of treated cancer cells analyzed by Transmission Electron Microscopy (TEM) highlighted the induction of a cytoplasmic vacuolization, thus suggesting paraptotic-like cancer cell death triggering.
Topics: Cell Death; Cell Line, Tumor; Cell Proliferation; Coordination Complexes; Copper; Crystallography, X-Ray; Humans; Ligands; Models, Molecular; Molecular Structure; Pyrazoles; Spheroids, Cellular; Triazoles
PubMed: 31067640
DOI: 10.3390/molecules24091761 -
Archiv Der Pharmazie Aug 2020Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones...
Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including H and C nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization-mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e, 3u, and 7h showed an MIC value of 3.125 µg/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between -7.047 and -9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrödinger software, and these compounds exhibited good pharmacological and oral absorption properties.
Topics: Antitubercular Agents; Chalcones; Coumarins; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Quinolines; Software
PubMed: 32484273
DOI: 10.1002/ardp.202000077 -
Organic Letters Nov 2013A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This...
A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a great diversity of phosphorus substituents on the different carbons of the pyrazole ring in a one-step process.
Topics: Catalysis; Molecular Structure; Organophosphonates; Organophosphorus Compounds; Palladium; Phosphines; Pyrazoles
PubMed: 24131425
DOI: 10.1021/ol402717b