Antifolates are a class of drugs used as antibacterial, antiparasitic, and anticancer agents. This review focuses on 2-substituted-mercapto-quinazolin-4(3H)-one analogues as dihydrofolatereductase (DHFR) inhibitors. Several research work have concluded a structural model for this class of 2-thio-quinazoline derivatives to get compounds with remarkable biological activity. The pattern and orientation of the p-system substitutions with regard to the quinazoline nucleus manipulate the activity. The application of the obtained model criteria produced compounds 18, 20 and 21, which proved to be 4-8 times more active than the reference drug methotrexate (MTX, 1).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1389557521666210304105736 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Resistance 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 PDFDihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.
Eur J Med Chem
February 2025
Natural and Medical Sciences Research Center, University of Nizwa, P.O. Box 33, 616, Nizwa, Oman. Electronic address:
In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.
View Article and Find Full Text PDFMolecular modeling, synthesis and biological evaluation of caffeic acid based Dihydrofolate reductase inhibitors.
BMC Chem
December 2024
Laboratory of Preservation Technology and Enzyme Inhibition Studies, Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.
Dihydrofolate reductase (DHFR) is an enzyme that plays a crucial role in folate metabolism, which is essential for cell growth and division. DHFR has been identified as a molecular target for numerous diseases due to its significance in various biological processes. DHFR inhibitors can disrupt folate metabolism by inhibiting DHFR, leading to the inhibition of cell growth.
View Article and Find Full Text PDFRecent Cutting-Edge Designing Strategies for Mtb-DHFR Inhibitors as Antitubercular Agents.
Chem Biol Drug Des
December 2024
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
Tuberculosis (TB) is an obstinate and infectious disease requiring a relatively longer treatment duration than other bacterial infections. The current treatment regime is prolonged and cumbersome, with adverse effects, often leading to nonadherence. The upsurge in TB's multidrug-resistant and extensively drug-resistant strains with evolved resistance to existing drugs has compounded the problems.
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!