Three synthesized series of compounds based on a thiazolidine core allowed identification of potent inhibitors of thymidylate synthase X. The evaluation of the catalytic activity of the enzyme in the presence of these molecules revealed two distinct classes of compounds that inhibit ThyX with submicromolar concentrations, which could lead, after optimization, to effective inhibitors with potential biomedical interest.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2008.04.080 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Beyond Chemotherapy: Exploring 5-FU Resistance and Stemness in Colorectal Cancer.
Eur J Pharmacol
January 2025
School of Biotechnology, KIIT Deemed to be University, Bhubaneswar - 751024, Odisha, India. Electronic address:
Colorectal cancer (CRC) remains a significant global health challenge, demanding continuous advancements in treatment strategies. This review explores the complexities of targeting colorectal cancer stem cells (CSCs) and the mechanisms contributing to resistance to 5-fluorouracil (5-FU). The efficacy of 5-FU is enhanced by combination therapies such as FOLFOXIRI and targeted treatments like bevacizumab, cetuximab, and panitumumab, particularly in KRAS wild-type tumors, despite associated toxicity.
View Article and Find Full Text PDFRepurposing the Antidiabetic Drugs Glyburide, Gliquidone, and Glipizide in Combination with Benznidazole for Infection.
Pharmaceuticals (Basel)
December 2024
Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Infection with the protozoan parasite causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency of these drugs for its safer use. : Glyburide, glipizide, and gliquidone, hypoglycemic drugs for diabetes treatment, were previously predicted to bind to dihydrofolate reductase-thymidylate synthase from by in silico docking analysis; they also showed antiproliferative effects against epimastigotes, the stage of the insect vector.
View Article and Find Full Text PDFResistance of to Trimethoprim: Insights into Genes Encoding Dihydrofolate Reductase, Thymidylate Synthase and Serine Hydroxymethyltransferase in the Rickettsiales.
Insects
December 2024
Department of Entomology, University of Minnesota, St. Paul, MN 55108, USA.
Bacterial and eukaryotic dihydrofolate reductase (DHFR) enzymes are essential for DNA synthesis and are differentially sensitive to the competitive inhibitors trimethoprim and methotrexate. Unexpectedly, trimethoprim did not reduce abundance, and the Stri DHFR homolog contained amino acid substitutions associated with trimethoprim resistance in . A phylogenetic tree showed good association of DHFR protein sequences with supergroup A and B assignments.
View Article and Find Full Text PDFAssessment of Erythrocytes Methotrexate Polyglutamate Three Levels in Psoriatic Patients Treated with Methotrexate Monotherapy and Their Association with Disease Response.
Indian J Clin Biochem
January 2025
Department of Dermatology, JIPMER, Puducherry, 06 India.
Unlabelled: Methotrexate is used to manage moderate to severe psoriasis and psoriatic arthritis. Methotrexate acts by inhibiting the enzymes involved in nucleotide synthesis. Methotrexate polyglutamates (MTXPGs) have a higher potency to inhibit Dihydrofolate reductase (DHFR), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC), and thymidylate synthase (TS), compared to naïve methotrexate.
View Article and Find Full Text PDFCytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells involving ribonucleotides in DNA.
Sci Rep
January 2025
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, N-7491, Trondheim, Norway.
The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!