The application of gold in medicine can be traced back several thousand years and Au(i) compounds have been used in the treatment of rheumatoid arthritis since the last century. Recently research into gold-based drugs for a number of human diseases has seen a renaissance due to their markedly different modes of action with respect to the classical platinum chemotherapeutic compounds. Within this research area, organometallic gold complexes have been particularly explored, mainly due to their higher stability in physiological conditions guaranteed by the presence of a direct Au-C bond. Thus, a number of compounds have been tested for their uses as anticancer, antibacterial, antiprotozoal as well as anti-HIV agents. In this review a selection of the main results obtained on the synthesis, chemical properties and biological activities of two of the most explored families of organometallics - Au(i) N-heterocyclic carbenes (NHCs) and cyclometalated Au(iii) compounds - are summarized. Their structure-activity relationships and modes of action at the cellular level are also discussed, which constitute the basis for future drug design.
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http://dx.doi.org/10.2533/chimia.2017.92 | DOI Listing |
Nucleic Acids Res
January 2025
Single-Molecule and Cell Mechanobiology Laboratory, Daejeon, 34141, South Korea.
Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability.
View Article and Find Full Text PDFHeliyon
January 2025
Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Complex Cibinong Science Center-BRIN, Cibinong, 16911, Jawa Barat, Indonesia.
The escalating concerns about the environmental and health impacts of synthetic pesticides have intensified the search for sustainable and effective alternatives. Cinnamon oil, derived from the bark of Cinnamomum species, has emerged as a promising candidate in this arena due to its potent biopesticidal properties. This review explores the multifaceted role of cinnamon oil in agricultural pest management, emphasizing its potential to contribute significantly to food security.
View Article and Find Full Text PDFNat Biotechnol
January 2025
Department of Biomedicine, University of Basel, Basel, Switzerland.
Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.
View Article and Find Full Text PDFAquat Toxicol
January 2025
Unité écotoxicologie des substances et des milieux, Institut National de l'Environnement Industriel et des Risques (INERIS), 60550 Verneuil-en-Halatte, France. Electronic address:
Facing the need for alternative models allowing assessment of metabolic-endocrine disrupting chemicals (MDCs), especially in poorly investigated tissues such as the intestine, we recently developed a transgenic zebrafish embryo in vivo model, tg(cyp3a65:GFP), expressing the Green Fluorescent Protein (GFP) under the control of the zebrafish cyp3a65 promoter, ortholog of human cyp3a4, a gene coding for a key enzyme of intestinal xenobiotic and endobiotic metabolism. In this study, we aimed to better understand the regulation of cyp3a65 expression by zfPXR, zfAhR2, and zfGR zebrafish orthologs of well-known human xenosensors PXR and AhR, and steroid nuclear receptor GR. For this purpose, we performed zebrafish embryo tg(cyp3a65:GFP) (co)exposures to a variety of agonists (clotrimazole, TCDD, fluticasone propionate) and antagonists (econazole nitrate, CH223181, RU486), which were characterized using in vitro zebrafish reporter gene assays.
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