Design, Synthesis, Anti-Varicella-Zoster and Antimicrobial Activity of (Isoxazolidin-3-yl)Phosphonate Conjugates of N1-Functionalised Quinazoline-2,4-Diones
Magdalena Łysakowska,
Iwona E. Głowacka,
Graciela Andrei,
Dominique Schols,
Robert Snoeck,
Paweł Lisiecki,
Magdalena Szemraj,
Dorota G. Piotrowska
Affiliations
Magdalena Łysakowska
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Iwona E. Głowacka
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Graciela Andrei
Laboratory of Virology and Chemotherapy, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, B-3000 Leuven, Belgium
Dominique Schols
Laboratory of Virology and Chemotherapy, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, B-3000 Leuven, Belgium
Robert Snoeck
Laboratory of Virology and Chemotherapy, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, B-3000 Leuven, Belgium
Paweł Lisiecki
Department of Pharmaceutical Microbiology and Microbiological Diagnostics, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Magdalena Szemraj
Department of Pharmaceutical Microbiology and Microbiological Diagnostics, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Dorota G. Piotrowska
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
Dipolar cycloaddition of the N-substituted C-(diethoxyphosphonyl)nitrones with N3-allyl-N1-benzylquinazoline-2,4-diones produced mixtures of diastereoisomeric 3-(diethoxyphosphonyl)isoxazolidines with a N1-benzylquinazoline-2,4-dione unit at C5. The obtained compounds were assessed for antiviral and antibacterial activities. Several compounds showed moderate inhibitory activities against VZV with EC50 values in the range of 12.63–58.48 µM. A mixture of isoxazolidines cis-20c/trans-20c (6:94) was found to be the most active against B. cereus PCM 1948, showing an MIC value 0.625 mg/mL, and also was not mutagenic up to this concentration.
