Novel triazine dimers with potent antitrypanosomal activity

作者：Venkatraj Muthusamy; Salado Irene G; Heeres Jan; Joossens Jurgen; Lewi Paul J; Caljon Guy; Maes Louis; Van der Veken Pieter; Augustyns Koen^*

来源：European Journal of Medicinal Chemistry, 2018, 143: 306-319.

DOI：10.1016/j.ejmech.2017.11.075

• Trypanosoma brucei
• Dimer
• Microsomal stability
• Phenotypic screening

Human African trypanosomiasis (HAT), also known as sleeping sickness is a parasitic disease transmitted by the bite of the 'Glossina' insect, commonly known as the tsetse fly. This disease affects mostly poor populations living in remote rural areas of Africa. Untreated, it is usually fatal. Currently, safe and effective treatments against this disease are lacking. Phenotypic screening of triazine non-nucleoside HIV-1 reverse transcriptase inhibitors (monomers) resulted in potent and selective antitrypanosomal compounds. This serendipitous discovery and the presence of dimers in many compounds active against these neglected tropical diseases prompted us to investigate antitrypanosomal activity of triazine dimers. Optimization of the triazine dimers resulted in 3,3'-(((ethane-1,2-diylbis(azanediyl))bis(4-(mesityloxy)-1,3,5-triazine-6,2-diyl))bis(azanediyl))dibenzonitrile (compound 38), a compound with very potent in vitro and moderate in vivo antitrypanosomal activity.

• 出版日期2018-1-1