Atividade antitumoral e antimicrobiana de alcaloides bisbenzilisoquinol?nicos de Cissampelos sympodialis Eichler (Menispermaceae)

Cissampelos sympodialis (Menispermaceae) ? uma esp?cie popularmente conhecida como ?milona?, utilizada na medicina popular, especialmente para afec??es do trato respirat?rio. Apesar de in?meras a??es dos extratos e de alcaloides bisbenzilisoquinol?nicos desta esp?cie j? terem sido relatados, estes ainda n?o haviam sido testados de forma sistem?tica para atividade antitumoral ou antimicrobiana. Assim, o objetivo deste estudo foi realizar uma revis?o sistem?tica das atividades antitumoral e antimicrobiana de alcaloides bisbenzilisoquinol?nicos e testar os alcaloides isolados frente ?s atividades mencionadas. Para isso, a fra??o de alcaloides dos rizomas foi preparada e subfracionada utilizando cromatografia l?quida preparativa. Os alcaloides isolados (warifte?na e metilwarifte?na) foram caracterizados por t?cnicas espectrom?tricas. Ensaios de atividade antitumoral foram realizados em linhagens HepG2, de tumor hep?tico, e HCT116, de tumor de c?lon. A atividade antimicrobiana foi testada frente a v?rias esp?cies bacterianas gram positivas e gram negativas. A revis?o sistem?tica identificou 38 estudos relativos ? atividade antitumoral, envolvendo 31 alcaloides bisbenzilisquinol?nicos diferentes. Os resultados mais promissores envolvem a a??o da tetrandrina em c?ncer de colo uterino, c?lon, e mama, com CI50 < 2 ?M. Com rela??o ? atividade antibacteriana e antif?ngica, um n?mero bem menor de artigos foi identificado, envolvendo nove alcaloides, e 18 esp?cies bacterianas, sendo Bacilus subtilus, Mycobacterium tuberculosis e Staphylococcus aureus aquelas com mais cepas testadas com maior n?mero de ABBI diferentes. Foram identificados trabalhos com seis esp?cies f?ngicas, sendo a C. albicans a ?nica testada com dois ABBI diferentes, e demais esp?cies apenas com um ABBI. A subfra??o de alcaloides de C. sympodialis codificada como P04 (ainda n?o identificada) apresentou resultado promissor frente ? linhagem HCT116, com CI50 23,68 ?g/mL, por?m nenhuma das fra??es triadas nesse estudo apresentou resultado promissor para a linhagem HepG2. A warifte?na foi efetiva contra tr?s esp?cies bacterianas, E. coli, S. agalactiae e K. oxytoca, na concentra??o de 200 ?M.Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM)Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2020.Cissampelos sympodialis (Menispermaceae) is a species popularly known as ?milona?, and is used in traditional medicine specially for respiratory tract diseases. Despite the reported pharmacological actions of extracts and isolated bisbenzylisoquinoline alkaloids from the species, these were not tested in a systematic way for their antitumor or antimicrobial effects. Thus, the aim of this work was to perform a systematic review of the literature for the antitumor and antimicrobial activity of bisbenzylisoquinoline alkaloids and to test the isolated alkaloids from the species for these biological activities. The total alkaloid fraction from the rhizomes was prepared and fractionated using preparative high-performance liquid chromatography. The isolated alkaloids (warifteine and methylwarifteine) were characterized by spectrometric techniques. Antitumor assays were performed using the following cell lines: HepG2, from liver tumor and HCT116, from colon tumor. The antimicrobial activity was tested against several gram-positive and gram-negative bacteria. The systematic review of the literature identified 38 studies regarding antitumor activity of bisbenzylisoquinoline alkaloids, involving 31 different alkaloids. The most promising studies for antitumor effect are those of tetrandrine against uterine, colon and breast cancer, with IC50 < 2 ?M. As for antibacterial and antifungal activity, the number of studies was considerably lower, involving nine alkaloids and 18 bacterial strains, with Bacilus subtilus, Mycobacterium tuberculosis and Staphylococcus aureus the species with more strains tested and with a larger number of different alkaloids tested. We identified studies involving six types of fungi, and C. albicans was the only one tested with more than one alkaloid, while the other fungi types were tested against only one substance. The Cissampelos sympodialis alkaloid subfraction coded as P04 (not yet identified) showed activity against HCT116 tumor cell line, with IC50 23.68 ?g/mL, however none of the fractions or isolated alkaloids were active against the HepG2 cell line. Warifteine was effective against three bacterial strains, E. coli, S. agalactiae e K. oxytoca, at 200 ?M