Synthesis of 5-[alkoxy-(4-nitro-phenyl)-methyl]-uridines and study of their cytotoxic activity

• Published in: European journal of medicinal chemistry 2010-09, Vol.45 (9), p.3588-3594
• Main Authors: Brulíková, Lucie, Džubák, Petr, Hajdúch, Marián, Lachnitová, Lenka, Kollareddy, Madhusudhan, Kolář, Milan, Bogdanová, Kateřina, Hlaváč, Jan
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacteria - drug effects; Biological and medical sciences; Cell Line, Tumor; Cytotoxic activity; General aspects; Humans; Inhibitory Concentration 50; Medical sciences; Pharmacology. Drug treatments; Ribonucleosides; Uracils; Uridine - analogs & derivatives; Uridine - chemical synthesis; Uridine - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.05.003

A series of uridine analogues modified at the 5-position with the 5-[alkoxy-(4-nitrophenyl)-methyl] moiety was synthesized. Nucleosides were formed as a mixture of two diastereoisomers, which were separated and tested for their cytotoxic activity in vitro against different cancer cell lines and for antimicrobial activity. Relationships between structure and the above mentioned activities were studied. The cytotoxic activity was slightly increased in some cases by transformation of bases to nucleosides. Depending on the length of the alkyl chain increased cytotoxic and antimicrobial activity were noted. The cytotoxic activity of the nucleosides was not due to cell cycle alterations, DNA and/or RNA synthesis. The synthesis, cytotoxic activity, DNA/RNA synthesis inhibition and apoptosis induction of target compounds in their both diastereoisomeric forms were studied. [Display omitted]