Substituted 7-deazapurine ribonucleosides as antiparasitic agents
Trypanosoma brucei species cause Human African Trypanosomiasis – also known as sleeping sickness, which is one of the most neglected tropical diseases. Trypanosoma can become resistant to currently used drugs, therefore new antiparasitic agents are of high interest. Besides, the novel drugs could replace the medicaments with serious side effects.
The research group of Michal Hocek from IOCB Prague in collaboration with Alena Zíková from the Institute of Parasitology reported a series of 7-methyl-7-deazapurine ribonucleosides bearing different substituents at position 6 of the heterocycle. These molecules displayed an antiparasitic effect and low toxicity. The most active compounds were the 6-alkoxy derivatives showing inhibition at nanomolar concentrations.
The article in ACS Infectious Diseases describes the design and synthesis of substituted ribonucleosides, their antitrypanosomal activity, and toxicological studies.
Read the paper:
- Perlíková, P.; Krajczyk, A.; Doleželová, E.; Slapničková, M.; Milisavljevic, N.; Slavětínská, L. P.; Tloušt’ová, E.; Gurská, S.; Džubák, P.; Hajdúch, M.; Zíková, A.; Hocek, M. Synthesis and Antitrypanosomal Activity of 6-Substituted 7-Methyl-7-deazapurine Nucleosides. ACS Infectious Diseases 2021, 7, 917-926. https://doi.org/10.1021/acsinfecdis.1c00062