Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity at 0.275, 0.5 and 5microM of oxime, respectively (p< or =0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25microM) (p< or =0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p< or =0.05). The oxime showed a significant inhibitory effect on sigma-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p< or =0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the delta-aminolevulinate dehydratase (delta-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.
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http://dx.doi.org/10.1016/j.cbi.2008.09.028 | DOI Listing |
J Med Chem
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Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Based on our previous work, a series of imidazole-based small molecules were designed and synthesized as HDAC3 inhibitors. Among them, compound showed selective HDAC3 inhibition activity with an IC of 53 nM (SI = 75 for HDAC3 over HDAC1). Further studies revealed that could dose-dependently induce the expression of PD-L1 in MC38 cells by activating the PD-L1 transcription.
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Cleveland Clinic, Cleveland, OH, United States.
Epidermal growth factor receptor (EGFR) is a highly expressed driver of many cancers, yet the utility of EGFR inhibitors is limited to cancers that harbor sensitizing mutations in the EGFR gene due to dose limiting toxicities. Rather than conventionally blocking the kinase activity of EGFR, we sought to reduce its transcription as an alternative approach to broaden the therapeutic window for EGFR inhibitors targeting wildtype or mutant EGFR. We found that YES1 is highly expressed in triple negative breast cancer (TNBC) and drives cell growth by elevating EGFR levels.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
College of Life Science, South-Central Minzu University, No. 182, Minyuan Road, Hongshan District, Wuhan 430074, China.
Microbiota dysfunction induces intestinal disorders and neurological diseases. Mannuronate oligosaccharides (MAOS), a kind of alginate oligosaccharide (AOS), specifically exert efficacy in shaping gut microbiota and relieving cognitive impairment. However, the key regulatory factors involved, such as the specific strains and metabolites as well as their regulatory mechanisms, remain unclear at present.
View Article and Find Full Text PDFAntibodies (Basel)
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MacroGenics Inc., Rockville, MD 20850, USA.
Bispecific antibodies represent a promising class of biologics for cancer treatment. However, their dual specificity and complex structure pose challenges in the engineering process, often resulting in molecules with good functional but poor physicochemical properties. To overcome limitations in the properties of an anti-5T4 x anti-CD3 (α5T4 x αCD3) DART molecule, a phage-display method was developed, which succeeded in simultaneously engineering cross-reactivity to the cynomolgus 5T4 ortholog, improving thermostability and the elevating expression level.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Radiopharmaceutical theranostics holds significant promise in tumor diagnosis and treatment, but suboptimal tumor uptake and retention remain a persistent limitation. We have conjugated a unique albumin binder to our previously developed heterodimeric precursor HX01 and achieved a novel precursor L6, aiming to prolong circulation time and enhance tumor accumulation and retention. However, we observed that the NGR sequence of L6 was gradually rearranged to iso-DGR under alkaline conditions, resulting in decreased stability.
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