Synthesis and trypanocidal activity of 7, 2'-dioxygenated isoflavones and oxypropanolamine derivatives

Abstract

7,2'-Di-hidroxiisoflavona apresentou atividade contra tripomastigotas sanguíneos do Trypanosoma cruzi, agente etiológico da doença de Chagas, o que motivou a síntese de derivados anfifílicos de potencial utilização como quimioprofilático para esterilização de sangue para transfusão. Esta substância foi obtida por desmetilação da 7-hidroxi-2'-metoxiisoflavona, sintetizada via desoxibenzoína, seguindo-se eterificação com epicloridrina e abertura do anel oxirânico com dietilamina para levar à 7-oxipropanolamina, a qual, por tratamento com iodeto de metila, forneceu o sal de amônio correspondente. Nos ensaios in vitro com tripomastigotas sanguíneos do T. cruzi, a 7-hidroxi-2'-metoxiisoflavona foi inativa e a 7-oxipropanolamina foi mais ativa do que a 7,2'-di-hidroxiisoflavona. Já o sal de amônio, não só não eliminou completamente o parasita do sangue como causou lise total dos eritrócitos. Portanto, o sal de amônio não é adequado para o uso como profilático na transmissão do T.cruzi por transfusão sangüínea. A atividade tripanossomicida da 7,2'-di-hidroxiisoflavona e do seu derivado 7oxipropanolamina estimulam a avaliação in vivo destas substâncias como potenciais quimioterápicos para tratamento da doença de Chagas, sendo necessários alguns gramas destas substâncias que poderão ser obtidos pelos processos simples descritos neste trabalho. 7, 2'-Dihydroxyisoflavone was shown to be active against the bloodstream trypomastigote form of Trypanosoma cruzi, the etiologic agent of Chagas' disease. Amphiphilic derivatives of this isoflavone were synthezised aiming to obtain hydrosoluble compounds of potential use as prophylactic agents to be added to blood for transfusion. This isoflavone was obtained by demethylation of 7-hydroxy-2'-methoxyisoflavone that was synthesized via the intermediate deoxybenzoin. Its reaction with epichlorohydrin, followed by aminolysis with diethylamine, afforded the 7-oxypropanolamine which on treatment with methyl iodide gave the corresponding ammonium salt. The 7-hydroxy-2'methoxyisoflavone was inactive in the in vitro assays, the 7-oxypropanolamine was more active than 7, 2'-dihydroxyisoflavone while the ammonium salt has not eliminated the parasite from the blood besides causing total lysis of the erythrocytes. The simple synthetic procedures described in the present paper can be used to provide gram quantities of 7, 2'-dihydroxyisoflavone and its 7oxypropanolamine derivative that should be further investigated in in vivo murine models as potential chemotherapeutic agents for treatment of Chagas' disease.

Synthesis and trypanocidal activity of ent-kaurane glycosides

“…Aiming to evaluate the preliminary trypanocidal activity of the main compounds of this work, in order to select the most potential active ones for the next in vivo assay, an in vitro evaluation of compounds 1-4, 9, 10a/b, 15 and 16 against trypomastigotes of T. cruzi (Y strain) was performed according to methodology previously described, 11,17,21,22 and the results are shown in Table 3.…”

Synthesis 3,4-Dimethoxybenzyl-2,4-Dihydroxyphenyl Ketone from Eugenol

“…Many synthetic methods have been developed for the synthesis of isoflavones, among others are compounds chalcone [6], [7], chromon [8] and deoksibenzoin [9], [10]. The two most popular synthesis of isoflavon are thedeoxybenzoine.…”

Direct Oxidation of Eugenol Using a Permanganate

“…Several researches followed this way. Faria et al (2005) (Whalley, 2000). Several methods have involved permanganate as an oxidizing agent such as Brown et al (1982), Wahyuningsih (1996) and Kusumaningsih (1999).…”