Related Experiment Video
Updated: Jan 4, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides
Dorota G Piotrowska1, Iwona E Głowacka1, Dominique Schols2
1Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
Abstract:
Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC50 values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).
Related Concept Videos
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Subviral Agents
DNA Base Pairing
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Retroviruses

