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New N-Alkylketonetetrahydroisoquinoline derivatives exhibits antitumor effect by HA-CD44 interaction inhibition in MDA-MB-231 breast cancer.
Bioorg Chem
January 2025
Department of Medicinal and Organic Chemistry and Excellence Research Unit of Chemistry Applied to Biomedicine and the Environment, Faculty of Pharmacy, University of Granada, Campus Cartuja s/n 18071 Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Avenida de Madrid, 15 18012 Granada, Spain. Electronic address:
Molecular interactions at the cell surface, in particular between hyaluronic acid (HA) and the cluster of differentiation 44 (CD44) receptor, are crucial in several biological processes and diseases such as cancer. Thus, inhibition of the HA-CD44 interaction has become a promising therapeutic strategy. Etoposide was the only antitumor compound known to inhibit the binding of CD44 to HA, thereby disrupting key functions that drive malignancy.
View Article and Find Full Text PDFPharmacological ascorbate combined with rucosopasem selectively radio-chemo-sensitizes NSCLC via generation of HO.
Redox Biol
January 2025
Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa College of Medicine, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA.
Differences in cancer and normal cell oxidative metabolism provide a unique therapeutic opportunity for developing combined modality approaches with redox-active small molecules as radio-chemosensitizers that are well-tolerated by normal tissues. Pentaazamacrocyclic Mn (II)-containing (MnPAM) superoxide dismutase (SOD) mimetics and pharmacological ascorbate given IV to achieve [mM] plasma levels (pharmacological ascorbate: P-AscH‾) have been shown to act individually as cancer cell radio- and chemosensitizers via the generation of HOin vivo. The current study shows that the combination of newly developed MnPAM dismutase mimetic, rucosopasem manganese (RUC) with P-AscH‾ radio-sensitizes non-small cell lung cancer cells (NSCLC) and increases steady state levels of intracellular HO with no additional toxicity to normal human bronchial epithelial cells (HBECs).
View Article and Find Full Text PDFComparative study of degree, neighborhood and reverse degree based indices for drugs used in lung cancer treatment through QSPR analysis.
Sci Rep
January 2025
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11461, Riyadh, Saudi Arabia.
Quantitative structure-property relationship (QSPR) modeling has emerged as a pivotal tool in the field of medicinal chemistry and drug design, offering a predictive framework for understanding the correlation between chemical structure and physicochemical properties. Topological indices are mathematical descriptors derived from the molecular graphs that capture structural features and connectivity, playing a crucial role in QSPR analysis by quantitatively relating chemical structures to their physicochemical properties and biological activities. Lung cancer is characterized by its aggressive nature and late-stage diagnosis, often limiting treatment options and significantly impacting patient survival rates.
View Article and Find Full Text PDFLeflunomide-induced drug reaction eosinophilia systemic symptoms and haemophagocytic lymphohistiocytosis overlap syndrome with rheumatoid arthritis.
BMJ Case Rep
January 2025
Department of Infectious Diseases, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and haemophagocytic lymphohistiocytosis (HLH) are rare but severe immune-mediated diseases with overlapping clinical manifestations. We present a case of a woman in her late 40s with rheumatoid arthritis who developed DRESS/HLH overlap syndrome after starting hydroxychloroquine and leflunomide therapy. Despite corticosteroid treatment, her condition worsened, necessitating etoposide therapy.
View Article and Find Full Text PDFEtoposide-loaded lipopolymer nanoparticles promote Smac minetic activity against inhibitor of apoptosis protein for glioblastoma treatment.
Biomater Adv
January 2025
Department of Biomedical Sciences, National Chung Cheng University, Chia-Yi 62102, Taiwan, ROC.
Encapsulated BV6 and SM164, two bivalent second mitochondria-derived activator of caspase (Smac) mimetics, in etoposide (ETO)-lipopolymer nanoparticles (NPs) have been developed to deplete inhibitor of apoptosis proteins (IAP), impair DNA, and produce antagonistic effects on glioblastoma multiforme (GBM) in nude mice. The NPs, composed of cocoa butter (CB) and polyvinyl alcohol (PVA), were stabilized by glycerol monostearate and Pluronic F-127, and grafted with transferrin (Tf) and wheat germ agglutinin (WGA) to dock the blood-brain barrier (BBB) and degenerated dopaminergic neurons. The dual-targeting NPs increased the BBB permeability of BV6, SM164 and ETO via recognizing Tf receptor (TfR) and N-acetylglucosamine that are abundantly expressed on brain microvascular endothelial cells.
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