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Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1-pyrazol (), 3,5-dimethyl-4-(phenylselanyl)-1-pyrazole (), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1-pyrazole (), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1-pyrazole (), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1-pyrazole (), 3,5-dimethyl-4-(phenylthio)-1-pyrazole (), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1-pyrazole (), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1-pyrazole (), and 3,5-dimethyl-1-phenyl-1-pyrazole (). In vitro, 4-(arylcalcogenyl)-1-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds , , and presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds and presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds , , and (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds , , and did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.
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http://dx.doi.org/10.1139/cjpp-2019-0356 | DOI Listing |
Chem Biodivers
December 2024
Banaras Hindu University, Chemistry, institute of science, 221005, Varanasi, INDIA.
1,2,3-triazole-based ring connected with pyridazine, triazine, methyl pyrazole, diphenyl pyrazole, and pthalimide moieties through propylene linker have been synthesized for antidiabetic evaluation via click chemistry. The antidiabetic evaluations have been done by molecular docking studies and in- vitro tests and against the DPP-4 enzyme. The molecular docking studies have revealed that compounds 22, 23, 29, and 30 showed hydrogen bond with the DPP-4 enzyme while in vitro tests has revealed the compound 30 has (IC50 values 12.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2024
Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8s) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues.
View Article and Find Full Text PDFPhys Chem Chem Phys
December 2024
Laser Research Center, Vilnius University, Saulėtekio av. 10, LT-10223, Lithuania.
Pyrano[2,3-]pyrazole derivatives are a class of compounds exhibiting dual solvent-dependent fluorescence. This interesting and potentially useful optical property is attributed to the excited state intramolecular proton transfer (ESIPT). We have investigated excited state dynamics of these molecules in detail using femtosecond time-resolved fluorescence and transient absorption spectroscopy.
View Article and Find Full Text PDFJ Hematol Oncol
December 2024
Georgia Cancer Center, Augusta, GA, USA.
Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.
View Article and Find Full Text PDFJ Patient Rep Outcomes
December 2024
Eli Lilly and Company, Lilly Corporate Center DC 1730, Indianapolis, IN, 46285, USA.
Background: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).
Methodology: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline.
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