Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites. / Baliani, Alessandro; Peal, Valerie; Gros, Ludovic; Brun, Reto; Kaiser, Marcel; Barrett, Michael P.; Gilbert, Ian H.
In: Organic and Biomolecular Chemistry, Vol. 7, No. 6, 2009, p. 1154-1166.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Novel functionalized melamine-based nitroheterocycles: synthesis and activity against trypanosomatid parasites
A1 - Baliani,Alessandro
A1 - Peal,Valerie
A1 - Gros,Ludovic
A1 - Brun,Reto
A1 - Kaiser,Marcel
A1 - Barrett,Michael P.
A1 - Gilbert,Ian H.
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 - <p>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.</p>
AB - <p>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.</p>
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
M1 - Article
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
SN - 1477-0520
IS - 6
VL - 7
SP - 1154
EP - 1166
ER -