title: Structurally modified natural sesquiterpene lactones constitute effective and less toxic schistosomicidal compounds.
abstract: Sesquiterpene lactones are known to be active, but are also known to present high cytotoxicity. In the present work an evaluation of how slight structural alterations affect the cytotoxicity and the schistosomicidal activity of sesquiterpene lactones was undertaken. More specifically, we assessed the activity of budlein-A, a furanoheliangolide sesquiterpene lactone, and four of its derivatives. The structural modifications of budlein-A, presented in this work, diminished the cytotoxicity and changed the antiparasitary behavior of the molecule. They also provided data for a better understanding of the sesquiterpene lactone cytotoxicity. The establishment of the structures of three synthesized sesquiterpene lactones on the basis of NMR and HRESIMS data is also presented here. Complete and detailed (1)H and (13)C 1D and 2D NMR data, with measurements of all J values and all multiplicities clarified, are presented for five sesquiterpene lactones for the first time.
authors.affiliation: Departamento de Química, FFCLRP - Universidade de São Paulo, Brazil.
authors.forename: Daiane Cristina
authors.initials: DC
authors.lastname: Sass
authors.forename: Gustavo Oliveira
authors.initials: GO
authors.lastname: Morais
authors.forename: Ricardo Augusto Crema
authors.initials: RA
authors.lastname: Miranda
authors.forename: Lizandra Guidi
authors.initials: LG
authors.lastname: Magalhães
authors.forename: Wilson Roberto
authors.initials: WR
authors.lastname: Cunha
authors.forename: Raquel Alves
authors.initials: RA
authors.lastname: dos Santos
authors.forename: Nilton Syogo
authors.initials: NS
authors.lastname: Arakawa
authors.forename: Fernando Batista
authors.initials: FB
authors.lastname: Da Costa
authors.forename: Mauricio Gomes
authors.initials: MG
authors.lastname: Constantino
authors.forename: Vladimir Constantino Gomes
authors.initials: VC
authors.lastname: Heleno
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001700:Biomphalaria; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000977:Antiparasitic Agents; D001688:Biological Products; D007783:Lactones; D012556:Schistosomicides; D012717:Sesquiterpenes; C520233:budlein A