Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites

TY - JOUR

T1 - Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites

AU - Baliani, Alessandro

AU - Peal, Valerie

AU - Gros, Ludovic

AU - Brun, Reto

AU - Kaiser, Marcel

AU - Barrett, Michael P.

AU - Gilbert, Ian H.

PY - 2009

Y1 - 2009

N2 - Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.

AB - Human African trypanosomiasis (HAT), caused by the protozoan parasite Trypanosoma brucei spp., is a major health problem in sub-Saharan Africa. New drugs are urgently required for the disease. Selective uptake of toxic compounds into trypanosomes has been achieved by exploiting plasma membrane transporters. For example, the P2 aminopurine transporter, along with other transporters, selectively concentrates melamine and benzamidine moieties into trypanosomes. We have previously reported the use of the melamine motif to selectively target nitrofuran to the trypanosome. In this paper we report the further investigation of the structure activity relationships and the effect of the introduction of different functionalized substituents onto the melamine unit. Most of the compounds tested in vitro for their trypanocidal activity showed activities in the submicromolar range against T. b. rhodesiense.

KW - BRUCEI-BRUCEI

KW - NUCLEOSIDE TRANSPORTER

KW - AFRICAN TRYPANOSOMES

KW - CROSS-RESISTANCE

KW - DIAMIDINE DRUGS

KW - PENTAMIDINE

KW - ADENOSINE

KW - AFFINITY

KW - ADDUCTS

KW - CLONING

U2 - 10.1039/b813394h

DO - 10.1039/b813394h

M3 - Article

C2 - 19262935

SN - 1477-0520

VL - 7

SP - 1154

EP - 1166

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 6

ER -