Ten chalcones were synthesized and tested as potential leishmanicidal and trypanocidal agents. All tested compounds caused concentration-dependent inhibition of the in vitro growth of Leishmania braziliensis and Trypanosoma cruzi with no significant toxic effect towards host macrophages. Our results show that the positions of the substituents seem to be critical for their antiprotozoal activities.Among the kinetoplastid protozoa, which infect invertebrates, mammals, and plants, some species are of particular interest due to their medical importance. These include Trypanosoma cruzi (the agent of Chagas' disease), the African trypanosome responsible for sleeping sickness, and several species of Leishmania, which cause the various forms of leishmaniasis (9). The World Health Organization has identified Chagas' disease and leishmaniasis as major and increasing public health problems, particularly in Latin America (14,15,16,18). In spite of the socioeconomic importance of these tropical infectious diseases, efforts directed towards the discovery of new drugs and/or vaccines against them are underdeveloped (10, 13). In addition, most of the drugs currently in use (i) were developed several decades ago, (ii) show variable efficacy, (iii) have serious side effects, (iv) are expensive, (v) can require long-term treatment, (vi) may have low activity in immunosuppressed patients, and (vii) present and/or induce resistance in parasites (9, 10, 16). Thus, the need for the development of new, effective, cheap, and safe drugs for the treatment of leishmaniasis and Chagas' disease is very important.Chalcones, or 1,3-diaryl-2-propen-1-ones, are natural or synthetic compounds belonging to the flavonoid family. Chalcones possess a broad spectrum of biological activities, including antibacterial, anthelmintic, amoebicidal, antiulcer, antiviral, insecticidal, antiprotozoal, anticancer, cytotoxic, and immunosuppressive activities (for reviews, see references 11 and 12). The present study was designed to determine the in vitro leishmanicidal and trypanocidal activities of the 10 substitutioncontaining chalcones and to investigate the cytotoxic effects of these chalcones on mouse peritoneal macrophages in vitro.The chalcones used in the present study were synthesized in our laboratory by reaction of the appropriate aryl methyl ketone and aryl aldehyde (in a 1:1 ratio) in the presence of sodium hydroxide and ethanol. The products were then added to cooled diluted acetic acid according to the methodology previously described (8). The synthetic reaction gave substantial yields (55 to 98%) of all the chalcones, and these were characterized by 1 H nuclear magnetic resonance and infrared analyses and by microanalysis. The substitution-containing chalcones were dissolved in 0.5% Tween 80 in phosphatebuffered saline to prepare a working solution with a 0.1 M concentration before being passed through 0.22-m-pore-size Millipore filters. The structures of the chalcones are shown in Table 1.Cultures of promastigote forms of Leishmania braziliensis...

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Recebido em 15/4/02; aceito em 19/7/02 CHEMICAL ASPECTS AND THERAPEUTIC POTENTIAL OF CYCLIC IMIDES: A REVIEW. Cyclic imides consists of an important family of organic compounds with therapeutic potential. In this review, emphasis will be given to the chemical and biological aspects of several sub-classes of this family, incluing maleimides, succinimides, glutarimides, naphtalimides, etc. Additionally, will be focused the contribution of our research group in this field.Keywords: cyclic imides; synthesis; biological activities. INTRODUÇÃOA necessidade do desenvolvimento de novos fármacos, que sejam efetivos contra algumas patologias ainda sem tratamento adequado, e que possam substituir os existentes, porém a custos menores e dotados de menores efeitos adversos, tem impulsionado a comunidade científica a novas e incessantes pesquisas nesta área. A síntese orgânica tem contribuído significativamente neste aspecto, sendo responsável por cerca de 75% dos fármacos existentes no mercado farmacêutico 1,2 . Cabe ressaltar, porém, que muitos destes fármacos são oriundos de protótipos advindos de produtos naturais, especialmente de plantas, que têm, ao longo dos anos, possibilitado a descoberta de inúmeras moléculas bio-ativas 3-6 .Muitas classes de compostos orgânicos têm demonstrado promissores efeitos biológicos e a literatura científica relata um crescimento significativo de novas moléculas com potência similar ou superior àquela de um fármaco, sendo que muitos deles encontram-se em estudos pré-clínicos e clínicos avançados e pormenorizados. Entre estas substâncias, pode-se inserir as imidas cíclicas, alvo desta revisão.As imidas cíclicas são compostos que contém o grupo -CO-N(R)-CO-, sendo R um átomo de hidrogênio, grupo alquila ou grupo arila. Tais compostos podem ser divididos em sub-classes, incluindo as maleimidas, succinimidas, glutarimidas, ftalimidas, naftalimidas, etc., e seus respectivos derivados. Em 1970, Hargreaves e colaboradores 7 publicaram uma revisão abordando vários aspectos químicos, industriais e biológicos das imidas cíclicas. Nos últimos anos, esta classe de compostos tem ressurgido e atraído a atenção da comunidade científica, devido, principalmente, às suas potencialidades terapêuticas. Como exemplo, podemos citar o caso da talidomida (1) que apesar dos significativos efeitos adversos do passado, ocasionando praticamente 100% de teratogenicidade, mesmo em doses clí-nicas modestas, sendo sua indicação específica para uso na gravidez 8 , os recentes estudos têm evidenciado um possível uso desta substância para o tratamento de várias patologias incluindo o câncer 9-11 .Os departamentos de Química e Farmacologia da UFSC e o Núcleo de Investigações Químico-Farmacêuticas da UNIVALI iniciaram os estudos com esta classe de compostos a partir da descoberta do alcalóide natural filantimida (2), isolado das partes aéreas do Phyllanthus sellowianus 12 . Este composto, derivado da glutarimida, apresentou moderado efeito antimicrobiano 13 , antiespasmódico 14 e analgésico 15,16 , sendo então usado como mode...

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