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Synthesis and Biological Evaluation of Pyrazolylnaphthoquinones as New Potential Antiprotozoal and Cytotoxic Agents
Author(s) -
Sperandeo Norma R.,
Brun Reto
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200390016
Subject(s) - antiprotozoal , benznidazole , trypanosoma cruzi , chagas disease , trypanosoma brucei rhodesiense , trypanocidal agent , nifurtimox , plasmodium falciparum , pharmacology , african trypanosomiasis , trypanosoma brucei , cytotoxic t cell , in vitro , biology , trypanosomiasis , chemistry , virology , biochemistry , immunology , malaria , parasite hosting , world wide web , computer science , gene
The importance of American trypanosomiasis (Chagas' disease) in human pathology is widely known. The prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. In this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3‐aminopyrazole rings, were evaluated on Trypanosoma cruzi, the etiological agent of Chagas' disease. These activities were compared with those of three 5‐aminoisoxazole analogues. In addition, since these compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the activities of all six against Plasmodium falciparum, Trypanosoma brucei rhodesiense, and murine L ‐6 cells were also investigated. In the biological tests, five of the compounds showed significant in vitro trypanocidal activities against T. cruzi, with activities similar to that of benznidazole. Two of the 5‐aminoisoxazole analogues also showed good activities, in one case highly selective, against the K1 and NF54 strains of P. falciparum (IC 50 <0.12 μg mL −1 ). Three of the compounds were cytotoxic to murine L ‐6 cells (IC 50 =0.21–0.50 μg mL −1 ). The results suggested that the three pyrazolylnaphthoquinones and one of the 5‐aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively.