New heterocyclic compounds: Synthesis and antitrypanosomal properties

作者：Pomel S; Dubar F; Forge D; Loiseau P M; Biot C^*

来源：Bioorganic & Medicinal Chemistry, 2015, 23(16): 5168-5174.

DOI：10.1016/j.bmc.2015.03.029

• Quinoline
• Quinolone
• Benzimidazole
• Ferroquine
• Trypanosoma
• Sleeping sickness

Three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against Trypanosoma brucei gambiense. In the quinoline series, the metallo antimalarial drug candidate (ferroquine, FQ) and its ruthenium analogue (ruthenoquine, RQ, compound 13) showed the highest in vitro activities with IC50 values around 0.1 mu M. Unfortunately, both compounds failed to cure Trypanosoma brucei brucei infected mice in vivo. The other heterocyclic compounds were active in vitro with IC50 values varying from 0.8 to 34 mu M. One of the most interesting results was a fluoroquinolone derivative (compound 2) that was able to offer a survival time of 8 days after a treatment at the single dose of 100 mu mol/kg by intraperitoneal route. Although no clear-cut structure-activity relationships emerged, further pharmacomodulations are worth to be developed in this series.

• 出版日期2015-8-15