title: Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships.
abstract: Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972270, Brazil.
authors.forename: Thiago R
authors.initials: TR
authors.lastname: Morais
authors.affiliation: Centro de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP 01246902, Brazil.
authors.forename: Thais A
authors.initials: TA
authors.lastname: da Costa-Silva
authors.affiliation: Centro de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP 01246902, Brazil.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Centro de Parasitologia, Instituto Adolfo Lutz, São Paulo, SP 01246902, Brazil.
authors.forename: Samanta Etel T
authors.initials: SE
authors.lastname: Borborema
authors.affiliation: Centro de Ciências Aplicadas e Educação, Universidade Federal da Paraíba, Rio Tinto, PB 58297000, Brazil.
authors.forename: Marcus T
authors.initials: MT
authors.lastname: Scotti
authors.affiliation: Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG 38400902, Brazil.
authors.forename: Raquel Maria F
authors.initials: RM
authors.lastname: de Sousa
authors.affiliation: Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG 38400902, Brazil.
authors.forename: Ana Carolina C
authors.initials: AC
authors.lastname: Araujo
authors.affiliation: Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG 38400902, Brazil.
authors.forename: Alberto
authors.initials: A
authors.lastname: de Oliveira
authors.affiliation: Instituto de Química, Universidade Federal de Uberlândia, Uberlândia, MG 38400902, Brazil.
authors.forename: Sérgio Antônio L
authors.initials: SA
authors.lastname: de Morais
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972270, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP 09972270, Brazil. joao.lago@unifesp.br.
authors.forename: João Henrique G
authors.initials: JH
authors.lastname: Lago
mesh_terms: D027926:Anacardiaceae / Q000737:chemistry / Q000187:drug effects; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage; D000981:Antiprotozoal Agents / Q000008:administration & dosage; D014355:Chagas Disease / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007891:Leishmania / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D000977:Antiparasitic Agents; D000981:Antiprotozoal Agents; D010936:Plant Extracts; D014315:Triterpenes; C514393:tirucallane