The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.
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http://dx.doi.org/10.1016/j.bmcl.2014.08.007 | DOI Listing |
Future Med Chem
January 2025
Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Aim: With the aim of simultaneously modulating the epigenetic system and the protein kinase pathway, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases (ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimetastatic properties. We report here the rational design, synthesis, and biological evaluation of the HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).
Materials And Methods: A molecular docking study performed with the Gold software was used to develop HDAC/ROCK multitarget inhibitors.
Expert Opin Drug Saf
January 2025
Department of Pharmacy Practice and Science, R Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ, USA.
Background: Immune and targeted anti-cancer therapies are associated with an increased risk of infectious complications. The objectives of the present study were to evaluate the infectious complications associated with immune and targeted anti-cancer drugs.
Research Design And Methods: This was a retrospective for immune and targeted anti-cancer drugs submitted to the FDA Adverse Event Reporting System (FAERS) from 1996 to 20 March 2024.
Mol Cell Proteomics
January 2025
State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China; Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China; Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China. Electronic address:
Understanding dysregulated genes and pathways in cancer is critical for precision oncology. Integrating mass spectrometry-based proteomic data with transcriptomic data presents unique opportunities for systematic analyses of dysregulated genes and pathways in pan-cancer. Here, we compiled a comprehensive set of datasets, encompassing proteomic data from 2,404 samples and transcriptomic data from 7,752 samples across 13 cancer types.
View Article and Find Full Text PDFSci Rep
January 2025
The Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin repair. Exploring epigenetic regulation in adipose-derived stem cells (ADSCs) holds promise for improving skin injury treatments.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have been linked to protein lactylation in brain tissue, which has been shown to correlate with increased neuronal excitability. Ischemic stroke may promote neuronal glycolysis, leading to lactate accumulation in brain tissue.
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