Synthesis of amide derivatives of natural piperine and evaluation of insecticidal activity against larvae of Aedes aegypti

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2020-07-28T19:18:43Z No. of bitstreams: 1 2011 - Natalia Drumond Lopes.pdf: 1575636 bytes, checksum: 836e1f5b396f684793a2077a004262e8 (MD5) Made available in DSpace on 2020-07-28T19:18:43Z (GMT). No. of bitstreams: 1 2011 - Natalia Drumond Lopes.pdf: 1575636 bytes, checksum: 836e1f5b396f684793a2077a004262e8 (MD5) Previous issue date: 2011-08-19 Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior, CAPES, Brasil This work is part of a research project which investigates the use of abundant and accessible natural products in the synthesis of new molecules with potential biological activity. Piperine is an amide extracted with high yelds from the dry fruits of Piper nigrum. Recent studies, carried out in our laboratory, showed antiparasitic activity against Trypanossoma cruzi for piperine and for a series of its derivatives and analogues. Insecticidal activity against muscoid dipteran species was also observed, which had already been described in the literature for other piperine analogues. We describe the synthesis of a series of amide derivatives of piperine replacing the piperidine ring with other cyclic amides. We also describe another series developed by reduction of the double bonds of piperine together with reactions on the aromatic ring. All compounds were characterized by conventional methods of analysis (IR, NMR, GC-MS) and evaluated for their toxic effects against Aedes aegypti larvae through methodology recommended by the World Health Organization. The results obtained show that tetrahydropiperine possesses the best activity profile. The results are satisfactory considering other natural products with larvicidal activity reported in the literature. Este trabalho est? inserido numa linha de pesquisa que visa ? utiliza??o de produtos naturais abundantes e acess?veis como prot?tipo para s?ntese de novas mol?culas com potencial atividade biol?gica. A piperina ? a amida majorit?ria, extra?da com altos rendimentos dos frutos secos de Piper nigrum. Estudos realizados pelo nosso grupo de pesquisa constataram atividade antiparasit?ria frente ao Tripanosoma cruzi para piperina e uma s?rie de an?logos (amidas, oxadiaz?licos e mesi?nicos) e atividade inseticida contra esp?cies de d?pteros musc?ides. Al?m disso, a literatura apresenta diversos an?logos com atividade inseticida. Descrevemos aqui uma s?rie de amidas derivadas da piperina substituindo o anel piperid?nico por outras amidas c?clicas. Al?m de outra s?rie com redu??o das insatura??es da piperina e substitui??es no anel arom?tico. Todos os compostos foram caracterizados pelos m?todos convencionais de an?lise IV, CG-EM e RMN e avaliados quanto ? atividade inseticida frente a larvas de Aedes aegypti utilizando metodologia recomendada pela Organiza??o Mundial de Sa?de. Os resultados obtidos evidenciaram a tetraidropiperina (5-(benzo[d][1,3]dioxol-s-il)-1- (1-piperidinil)-pentamida) como a subst?ncia com melhor perfil de atividade. Os resultados s?o satisfat?rios diante de outros produtos naturais com atividade larvicida encontrados na literatura.