S?ntese de novas pirrolo [3,4-d]-pirimidinonas visando compostos com atividade antiparasit?ria

• Autor(a) principal: Rog?rio, Kamilla Rodrigues
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
• Texto Completo: https://tede.ufrrj.br/jspui/handle/jspui/3175
• topic: Rea??es multicomponentes; Biginelli; Mal?ria; Plasmodium falciparum; multicomponent reactions; Qu?mica

Malaria is characterized as a neglected disease, being responsible for more deaths worldwide than other neglected ones, with few treatment options which are often toxic. The search for new effective antimalarial drugs that present low toxicity is vital in the current world scenario. Heterocycles such as Dihydropyrimidinones (DHPM) synthesized by the Biginelli mulcitomponent reaction have emerged as potential candidates for antimalarials as well as bicyclic compounds synthesized from them. Those multicomponent reactions stand out mainly for being clean reactions (not generating by-products), versatile (systematic variation of reagents) and susceptible to automation processes. Two families of compounds were synthesized using the classical Biginelli protocol and its activities were evaluated against Plasmodium falciparum blood form parasites and its cytotoxicity was tested with Baseline kidney African Green Monkey (BGM) cell culture. The synthetic route chosen was effective, leading to products with high purity and moderate yields. After the pharmacological assays, three (3) DHPM derivatives were identified as active against the parasite, presenting low toxicity and a selectivity index greater than 10, thus becoming potential prototypes structural optimization in order to improve the activity.