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ChemMedChem Oct 2020In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro...
In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC =0.78±0.01 μM), HT29 (IC =0.92±0.15 μM) and K562 (IC =47.25±1.24 μM) cell lines, prompted us to further investigate the antitumor effects of the best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). In cell-cycle analysis, S2 was found to disrupt the growth phases with increased cell population in G /G phase and decreased cell population in G /M phase. The excellent in vitro effects were also supported by inhibition of anti-apoptotic protein Bcl-2. In vivo tumor regression studies of S2 in HT29 xenograft nude mice, exhibited equivalent and promising tumor regression with maximum TGI, 66 % (i. p. route) and 60 % (oral route) at 50 mg kg dose by both the routes, indicating oral bioavailability and antitumor efficacy. These findings advocate that hybridization of pyrazoline and pyrrolidine-2,5-dioes holds promise for the development of more potent and less toxic anticancer agents.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Molecular Structure; Neoplasms, Experimental; Pyrazoles; Pyrrolidines; Structure-Activity Relationship
PubMed: 32715626
DOI: 10.1002/cmdc.202000458 -
Nucleosides, Nucleotides & Nucleic Acids 2005Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation,... (Review)
Review
Pyrazole nucleosides and condensed pyrazole nucleosides exhibit various biological activities. This article describes recent synthetic approaches to their preparation, chemical properties, biological activities, and structure-activity relationships, with emphasis to selected drugs or drug candidates. Two pyrazole C-nucleoside compounds pyrazofurin (pyrazomycin) and its alpha-epimer pyrazofurin B are active components of potent antivirals approved for therapeutic use in human medicine aimed against various diseases caused by DNA viruses.
Topics: Amides; Antimetabolites; Antiviral Agents; DNA Viruses; Pyrazoles; Ribonucleosides; Ribose; Structure-Activity Relationship; Virus Diseases
PubMed: 16270665
DOI: 10.1081/NCN-200067421 -
Bioorganic & Medicinal Chemistry Apr 20081-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These...
1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These imidazole derivatives showed an excellent antifungal activity against a clinical strain of Candida albicans and an interesting antitubercular activity against Mycobacterium tuberculosis H(37)Rv reference strain.
Topics: Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Hydrogen; Imidazoles; Magnetic Resonance Spectroscopy; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship
PubMed: 18321714
DOI: 10.1016/j.bmc.2008.02.055 -
Molecules (Basel, Switzerland) Jan 2021Carboxylation of bis(pyrazol-1-yl)alkanes by oxalyl chloride was studied. It was found that 4,4'-dicarboxylic derivatives of substrates with electron-donating methyl...
Carboxylation of bis(pyrazol-1-yl)alkanes by oxalyl chloride was studied. It was found that 4,4'-dicarboxylic derivatives of substrates with electron-donating methyl groups and short linkers (from one to three methylene groups) can be prepared using this method. Longer linkers lead to significantly lower product yields, which is probably due to instability of the intermediate acid chlorides that are initially formed in the reaction with oxalyl chloride. Thus, bis(pyrazol-1-yl)methane gave only monocarboxylic derivative even with a large excess of oxalyl chloride and prolonged reaction duration. An alternative approach involves the reaction of ethyl 4-pyrazolecarboxylates with dibromoalkanes in a superbasic medium (potassium hydroxide-dimethyl sulfoxide) and is suitable for the preparation of bis(4-carboxypyrazol-1-yl)alkanes with both short and long linkers independent of substitution in positions 3 and 5 of pyrazole rings. The obtained dicarboxylic acids are interesting as potential building blocks for metal-organic frameworks.
Topics: Alkanes; Crystallography, X-Ray; Dicarboxylic Acids; Molecular Conformation; Pyrazoles
PubMed: 33466823
DOI: 10.3390/molecules26020413 -
Chemical Communications (Cambridge,... Feb 2015A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new...
A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee).
Topics: Catalysis; Crystallography, X-Ray; Cyclization; Molecular Conformation; Pyrazoles; Silver; Stereoisomerism
PubMed: 25564304
DOI: 10.1039/c4cc09495f -
Bioorganic & Medicinal Chemistry Letters Sep 2021A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the...
Synthesis, docking, machine learning and antiproliferative activity of the 6-ferrocene/heterocycle-2-aminopyrimidine and 5-ferrocene-1H-Pyrazole derivatives obtained by microwave-assisted Atwal reaction as potential anticancer agents.
A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Ferrous Compounds; Humans; Machine Learning; Metallocenes; Microwaves; Molecular Docking Simulation; Molecular Structure; Pyrazoles; Pyrimidines; Structure-Activity Relationship
PubMed: 34217828
DOI: 10.1016/j.bmcl.2021.128240 -
Journal of Enzyme Inhibition and... Dec 20203-alkyl-5-aryl-1-pyrimidyl-1-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative...
3-alkyl-5-aryl-1-pyrimidyl-1-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC value of ()-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.
Topics: Dose-Response Relationship, Drug; Drug Discovery; Humans; Mitogen-Activated Protein Kinase 10; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Pyrazoles; Structure-Activity Relationship
PubMed: 31856610
DOI: 10.1080/14756366.2019.1705294 -
Molecules (Basel, Switzerland) Aug 2023On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF were designed and synthesized. Their...
On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF were designed and synthesized. Their chemical structures were characterized by H and C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds and exhibited higher activity against all the tested fungi, and displayed the highest activity against with an EC value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure-activity relationship analysis showed that, with respect to the R substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.
Topics: Antifungal Agents; Pyrazoles; Mass Spectrometry; Mycelium
PubMed: 37687108
DOI: 10.3390/molecules28176279 -
Discovery of Novel Triazole-Containing Pyrazole Ester Derivatives as Potential Antibacterial Agents.Molecules (Basel, Switzerland) Apr 2019To develop new antibacterial agents, a series of novel triazole-containing pyrazole ester derivatives were designed and synthesized and their biological activities were...
To develop new antibacterial agents, a series of novel triazole-containing pyrazole ester derivatives were designed and synthesized and their biological activities were evaluated as potential topoisomerase II inhibitors. Compound exhibited the most potent antibacterial activity with Minimum inhibitory concentration (MIC) alues of 4 µg/mL, 2 µg/mL, 4 µg/mL, and 0.5 µg/mL against , , , and , respectively. The in vivo enzyme inhibition assay displayed the most potent topoisomerase II (IC = 13.5 µg/mL) and topoisomerase IV (IC = 24.2 µg/mL) inhibitory activity. Molecular docking was performed to position compound into the topoisomerase II active site to determine the probable binding conformation. In summary, compound may serve as potential topoisomerase II inhibitor.
Topics: Anti-Bacterial Agents; DNA Gyrase; Esters; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Pyrazoles; Structure-Activity Relationship; Topoisomerase II Inhibitors; Triazoles
PubMed: 30987179
DOI: 10.3390/molecules24071311 -
European Journal of Medicinal Chemistry Mar 2019A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable...
A series of hybrids 10a-v based on coumarin/pyrazole oxime have been synthesized, and exhibit good to excellent antitumor activities. Compound 10n has shown remarkable anticancer effect on SMMC-7721 cells (IC = 2.08 μM), which is considerably lower than 5-FU (IC = 37.8 μM) and similar to ADM (IC = 2.67 μM), with little effect on normal hepatic cells LO2. Notably, the suppression experiments of metastatic activities reveal that 10n also displays significant anti-metastasis effects through inhibiting cell migration and invasion in highly metastatic SMMC-7721 cell line, and dose-dependently reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) procedure better than ADM. Finally, 10n also possesses low acute toxicity and potent tumor growth inhibitory property against SMMC-7721 cell lines in vivo. Our findings suggest that novel coumarin/pyrazole oxime hybrids are promising therapeutic agent candidates for further research.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Coumarins; Epithelial-Mesenchymal Transition; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Oximes; Pyrazoles; Structure-Activity Relationship; Transforming Growth Factor beta1
PubMed: 30739827
DOI: 10.1016/j.ejmech.2019.01.070