Background: Human African Trypanosomiasis (HAT, sleeping sickness) and Malaria
both are insect vectored tropical diseases. Only a couple of drugs is able to cure HAT, but all of
them are toxic, prone to resistance and require parenteral administration. Malaria is responsible for
high morbidity and mortality in humans. It is one of the global killers of children. Wide-spread
drug resistance against traditional therapeutics which were once highly effective makes them
almost useless. Therefore new drugs against both diseases are urgently needed.
Objective: Recently, we reported the synthesis and antiprotozoal activities of a number of new 2-
substituted 4-carbamoyl- and 4-aminoquinolines. This study focussed on the synthesis of novel
tetrazole derivatives which are linked to the quinoline core via a piperidine ring.
Methods: Novel compounds exhibiting a 7-chloroquinoline and a tetrazole ring were prepared via
Ugi-azide reaction. Modifications were restricted to the orientation and the substitution of the
linker. Compounds were tested for their activities against Trypanosoma brucei rhodesiense (STIB
900). Their antiplasmodial activities were determined against a sensitive (NF54) and a multiresistant
strain (K1) of Plasmodium falciparum.
Results: Eighteen tetrazole derivatives were prepared. The results of the biological tests were compared
with the activities of drugs in use and structure-activity relationships were discussed. Their
antitrypanosomal activities were only moderate. In contrast some of the compounds showed
promising activity against both strains of Plasmodium falciparum and good to excellent resistance
Conclusion: The antiplasmodial activities depended on the orientation of the 4-aminopiperidine
linker. Compounds with a tertiary amino group in position 4 of the quinoline ring exhibited equal
activity against both strains, whereas those with a secondary amino group were mainly active
against the sensitive strain.