title: Trypanocidal activity of 5,6-dihydropyran-2-ones against free trypomastigotes forms of Trypanosoma cruzi.
abstract: Sixteen 5,6-dihydro-2H-pyran-2-ones were evaluated in in vitro assay against trypomastigotes forms of Trypanosoma cruzi, the causative agent of Chagas' disease. A structure-activity relationship study (SAR) allowed us to establish the relevant structural features for the trypanocidal activity of goniothalamin analogues against T. cruzi. In fact, non-natural form of goniothalamin (ent-1) was threefold more potent than the natural one (1). In addition, we have identified analogues 9 and 10 (both displaying S configuration) as the highest potent compounds against T. cruzi with IC50=0.12 and 0.09 mM (IC50 value for crystal violet was 0.08 mM) whereas significantly lower toxicities were observed when these compounds were evaluated under LLC-MK2 lineage cells (1.38 and 4.89 mM, respectively). In addition, epoxides derivatives 12 and ent-12 were shown to be more potent than the corresponding stereoisomers 2 and ent-2 and non-natural argentilactone (ent-3, IC50=0.47 mM) was twofold more potent than natural argentilactone (3, IC50=0.94 mM).
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, UNICAMP, CP 6154, 13084-971 Campinas, SP, Brazil.
authors.forename: Angelo
authors.initials: A
authors.lastname: de Fátima
authors.forename: Cilene
authors.initials: C
authors.lastname: Marquissolo
authors.forename: Sergio
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: Ana Amélia
authors.initials: AA
authors.lastname: Carraro-Abrahão
authors.forename: Ronaldo Aloise
authors.initials: RA
authors.lastname: Pilli
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D011753:Pyrones; D014344:Trypanocidal Agents