thiourea and pyrazole

A series of six compounds (1a-f) possessing pyridine-pyrazole-benzenethiourea or pyridine-pyrazole-benzenesulfonamide scaffold were synthesized. The target compounds were screened to evaluate their inhibitory effect on human nucleotide pyrophosphatase/phosphodiesterase 1 and -3 (ENPP1 and ENPP3) isoenzymes. Compounds 1c-e were the most potent inhibitors of ENPP1 with sub-micromolar IC

Topics: Antineoplastic Agents; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Models, Molecular; Molecular Structure; Phosphoric Diester Hydrolases; Pyrazoles; Pyrophosphatases; Structure-Activity Relationship; Sulfonamides; Thiourea

In this work novel organic based compounds, acyl thiourea derivatives were synthesized and their anticancer activities were investigated. A new series of acyl thiourea derivatives containing pyrazole ring were prepared in good yield through one pot reaction of 4-benzoyl-1, 5-diphenyl-1H-pyrazole-3-carbonyl chloride with ammonium thiocyanate and various amines. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR and elemental analysis. Anticancer activities of synthesized compounds were evaluated on human colon, liver and leukemia cancer cell lines. Cell culture studies have demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity have altered in the presence of various side groups. These results confirm that novel pyrazolyl acyl thioureas derived compounds may be utilized for cancer treatment. Furthermore, these compounds have a great potential and significance for further investigations.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasms; Pyrazoles; Structure-Activity Relationship; Thiourea

It was discovered that a number of cyclin dependent kinase inhibitors containing the pyrazole core structure exhibited high inhibitory potency against broad-range CDKs and corresponding anti-proliferative activities. This information guided us to design and synthesize a series of 1,3-diphenyl-N-(phenylcarbamothioyl)-1H-pyrazole-4-carboxamide derivatives (5a-10d), and evaluate their biological activities as CDKs inhibitors. Among all the synthesized compounds, compound 10b inhibited CDK2 with an IC50 value of 25 nM, counteracting tumor cell proliferation of three cancer cell lines (H460, MCF-7, A549) in the micromolar range (from 0.75 μM to 4.21 μM), In addition, flow cytometry indicated that compound 10b could induce cycle G0/G1 phase arrest in A549 cells with a dose dependent. Taken together, compound 10b could be selected for further preclinical evaluation.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinases; Enzyme Activation; Humans; Inhibitory Concentration 50; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Pyrazoles; Thiourea

A series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives of biological interest have been prepared by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reaction of resulting amine with different arylisocyanates or arylisothiocyanates or arylsulfonyl chlorides. All the synthesized compounds (1-32) have been screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological evaluation study showed, the compounds 4, 5, 9, 11, 14 and 16 found to have promising anti-inflammatory activity (up to 61-85% TNF-α and 76-93% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (76% TNF-α and 86% IL-6 inhibitory activity at 1 μM). Compounds 24, 26, 27, 28 and 29 exhibited promising antimicrobial activity at MIC values ranging from 70 to 10 μg/mL against all the selected pathogenic bacteria and fungi.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Bacteria; Fungi; Microbial Sensitivity Tests; Pyrazoles; Structure-Activity Relationship; Sulfonamides; Thiourea; Urea

Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC₅₀ of 0.07 μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC₅₀ of 0.08 μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.

Topics: Antineoplastic Agents; Binding Sites; Cell Line, Tumor; Computer Simulation; ErbB Receptors; Humans; Neoplasms; Pyrazoles; Thioamides; Thiourea