Synthesis of 8.O.4 neolignans, derivatives and active analogues in Leishmania / Sintese de neolignanas 8.O.4 , derivados e analogos ativos em Leishmania

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Neolignans and lignans present significant biological and pharmacological activities. Chemically lignans are dimers derived from the oxidative coupling of cinnamic and/or cinnamyl alcohol, while neolignans derive from allyl and/or propenyl phenols. In this work, the synthesis of neolignans and correlated substances resulted from the condensation reactions between intermediate alpha-bromoketones with phenols and thiophenols. Sulphur oxidation reactions of certain neolignans analogues leading to neolignans-sulfoxide and sulfones respectively were also carried out, with the use of m-chloroperbenzoic and peracetic acids. Neolignans-alcohols were obtained using NaBH4 reductions while its acetate derivative was obtained from the acetylation reaction, with acetic anhydride and pyridine. The chiral reactions started with non-chiral ketones, which reacted with d/l-dimethyl-tartrate, providing chiral ketones that reacted with bromine, resulting in chiral a-bromoketone, these in their turn reacted with thiophenols leading to four chiral analogues. In previous studies conducted by our group, neolignans carrying oxygen and sulphur on the C-8 were essayed in Leishmania donovani showing that sulphur-neolignans had significant anti-leishmania activity. From the twenty-eight synthetic neolignans analogues containing O and S on the C-8 bridge obtained in this Master in Science project, twenty-four were racemic and four were chiral compounds. In cooperation with the UFRJ Carlos Chagas Institute, all substances were tested in vitro in Leishmania donovani and L. amazonensis. The results showed that four substances, two racemic and their respective chiral analogues, had significant anti-leishmania activity.

ASSUNTO(S)

leishmania neolignans leishmania leishmaniasis leishmaniose neolignanas

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