Natural products are regarded as major and important sources of molecules used in chemotherapy. Hypericum brasiliense Choisy, Hypericaceae, is an annual bush, native in the southern and southeastern Brazil. This species has been used in Brazilian folk medicine the anti-spasmodic and for the treatment of infectious diseases. H. brasiliense is chemically composed by flavonoids and xanthones. In addition, this species contain phloroglucinols, a class of substances with citotoxity effects against tumor cells lines. On the present study, hexanic extract and derivatives phloroglucinols obtained from H. brasiliense were tested against some human tumor cell lines. Hexanic extract presented a potent antiproliferative activity, with selective action on OVCAR-03 (ovarian), NCI-ADR/RES (ovarian resistant) and UACC-62 (melanoma) tumor cell lines. Uliginosin B was the most active derivative phloroglucinol, presenting selectivity against NCI-ADR/RES (resistant ovarian) and OVCAR-03 (ovarian) tumor cell lines. Analysis of the results suggests that phloroglucinol derivatives with isoprenyl unit closed in the 9' position increases antiproliferative activity. Furthermore, this study contributes to identification of anti-tumor molecules and valorization of Hypericum brasiliense. (C) 2013 Elsevier Editora Ltda. All rights reserved.235844847