Síntese total e investigação da atividade tripanocida e antimicrobiana de lignanas arilnaftalênicas

• Ano de defesa: 2008
• Autor(a) principal: Ruas, Marcelo Maia
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade de Franca; Brasil; Pós-Graduação; Programa de Mestrado em Ciências; UNIFRAN
• Palavras-chave em Português: Síntese; Lignanas arilnaftalênicas; Atividade tripanocida; Atividade antimicrobiana; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://repositorio.cruzeirodosul.edu.br/handle/123456789/820

The lignans have attracted much interest over the years on account of their large occurrence in several species of plants, their varied chemical structures and the many biological proprieties attributed to these compounds. Among the several biologically active lignans the podophyllotoxin and its derivatives have gained prominence due to its antitumoral properties. Another lignan that is attracting interest is the cubebin which presents several biological properties and which is also used in the synthesis of several biologically active derivatives. In the plant kingdom, lignans are found in a lot of families and the furofuranic are of greater occurrence. Several classes of lignans are the subject of many researchers’ studies like the phenyltetralin and the dibenzylbutyrolactone, however the class of arylnaphtalenics lignans despite presenting numerous biological properties have not been studied probably due to their low occurrence and studies are restricted only to members more known in the class which are justicidin, taiwanin and chinesin. There are synthetic proposals in literature to obtain the arylnaphalenic skeleton, though in most cases the yield in the following schedule is low and the compounds are obtained as mixtures of lactone and retrolactone. Thus, the aim of this work was to synthesize the largest possible number of arylnaphtalenics lignans and evaluate these compounds for trypanocidal and antimicrobial activity. The following path chosen for the synthesis of arylnaphtalenic lignans is described in the scheme (...) The choice of the study of these biological activities is based on the results presented in the literature from aryltetralinic lignans and dibenzylbutyrolactone. Based on the results presented from these lignans the same substitutes in the aromatic rings of biologically active compounds were also synthesized in the lignans arylnaphtalenic. The lignans were obtained in good yields from the reaction of Stobbe between ethyl succinate and an appropriate and aromatic aldehyde followed by more 5 steps reaction as described in Scheme above. The eight obtained arylnaphalenic lignans were evaluated for “in vitro” trypanocidal activity against forms trypoamastigotes of T. cruzi, however none of them showed activity and the values of % parasite lysis did not exceed 12% These same lignans were submitted to antimicrobial evaluation against oral pathogens Lactobacillus casei ATCC 11578, S.sanguinis ATCC S.mutans ATCC 10556 and 25175. The results of this biological evaluation showed that these lignans are inactive against the evaluated pathogens presenting MIC values greater than 400µM except the compound 8g which presented a value of 300µ for the pathogen Lactobacillus casei ATCC 11578 which is not considered an expressive value. Thus it is possible to conclude that unlike the aryltetralinic lignans and dibenzylbutyrolactone, the arylnaphtalenic lignans do not showed trypanocidal and antimicrobial activity. The inactivity of this class may be related to rigidity of the molecule by the presence of the naphthalenic ring that despite being flat given its double bonds it has no free rotation between carbons and, possibly, it cannot take an ideal conformation to connect in a given active site of the parasite as the other lignans already studied. Key words: Synthesis; arylnaphtalenic lignans; Tripanocidal activity; Antimicrobian activity