The administration of the lipophilic 3,7-bis-(4-trifluoromethylphenyl)- 1,5,3,7-dioxadiazocane (TFMPD) to rats induced the following effects on the biosynthesis of DNA in the liver, kidney, thymus and spleen: (a) The utilization of [3H]thymidine for the synthesis of liver DNA thymine was decreased after the administration of a single dose of the drug. The depression of the specific activities of DNA pyrimidines of liver DNA in experimental groups was observed also after an injection of [14C]orotic acid. (b) A decreased incorporation of labeled thymidine had occurred also in the spleen during the prereplicative period. Thereafter the specific activity of DNA thymine was higher than in the control group. (c) The observed mitogenic response in the spleen showed a protracted effect; after the administration of a single dose of the drug the specific activity of DNA thymine as well as the thymidine kinase activity of spleen cytosol have been rising up to the ninth day. The same holds true for DNA thymine of the thymus; the activity of thymidine kinase was not affected. (d) Both the single and repeated doses of TFMPD had no marked effect on the levels of microsomal cytochromes P-450 and b5 in the liver and kidney.
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http://dx.doi.org/10.1016/0300-483x(90)90053-j | DOI Listing |
J Phys Chem B
January 2025
School of the Chemical Science, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
The folding of the guanine repetitive region in the telomere unit into G-quadruplex (G4) by drugs has been suggested as an alternative approach for cancer therapy. Hydroxychloroquine (HCQ) and chloroquine (CQ) are two important drugs in the trial stage for cancer. Both drugs can induce the folding of telomere-guanine-rich sequences into G4 even in the absence of salt.
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January 2025
Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Carbonless DNA was designed by replacing all carbon atoms in the standard DNA building blocks with boron and nitrogen, ensuring isoelectronicity. Electronic structure quantum chemistry methods (DFT(ωB97XD)/aug-cc-pVDZ) were employed to study both the individual building blocks and the larger carbon-free DNA fragments. The reliability of the results was validated by comparing selected structures and binding energies using more accurate methods such as MP2, CCSD, and SAPT2+3(CCD)δ.
View Article and Find Full Text PDFSmall
January 2025
Department of Chemistry, McGill University, 801, Sherbrooke St. West, Montreal, QC, H3A 0B8, Canada.
Oligonucleotide therapeutics, including antisense oligonucleotides and small interfering RNA, offer promising avenues for modulating the expression of disease-associated proteins. However, challenges such as nuclease degradation, poor cellular uptake, and unspecific targeting hinder their application. To overcome these obstacles, spherical nucleic acids have emerged as versatile tools for nucleic acid delivery in biomedical applications.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.
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November 2024
Laboratory of Molecular and Cell Biology, Istituto Dermopatico Dell'Immacolata (IDI-IRCCS), 00167 Rome, Italy.
UVB radiation induces DNA damage generating several thymine photo-adducts (TDPs), which can lead to mutations and cellular transformation. The DNA repair pathways preserve genomic stability by recognizing and removing photodamage. These DNA repair side products may affect cellular processes.
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