Sesquiterpene lactones from Vernonia scorpioides and their in vitro cytotoxicity

• Published in: Phytochemistry (Oxford) 2010-09, Vol.71 (13), p.1539-1544
• Main Authors: Buskuhl, Humberto, de Oliveira, Fabio L., Blind, Luise Z., de Freitas, Rilton A., Barison, Andersson, Campos, Francinete R., Corilo, Yuri E., Eberlin, Marcos N., Caramori, Giovanni F., Biavatti, Maique W.
• Format: Article
• Language: English
• Subjects: Animals; anticarcinogenic activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apigenin; Asteraceae; Biological and medical sciences; Cell Line, Tumor; Chemical constitution; cultured cells; Cytotoxicity; Ethanol - chemistry; Ethyl caffeate; flowers; Flowers - chemistry; Fundamental and applied biological sciences. Psychology; genotoxicity; Glaucolide; Hirsutinolide; human cell lines; Humans; in vitro studies; Lactones - chemistry; leaves; Luteolin; Magnetic Resonance Spectroscopy; medicinal plants; Mice; Models, Molecular; Molecular Conformation; Mutagenicity Tests; neoplasms; Piptocarphol esters; Plant Extracts - chemistry; Plant Leaves - chemistry; Plant physiology and development; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenes - toxicity; sesquiterpenoid lactones; structure-activity relationships; Vernonia; Vernonia - chemistry; Vernonia scorpioides
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2010.06.007

This paper reports isolation of sesquiterpene lactones (SL), luteolin, apigenin, and ethyl caffeate. The investigation of the SL in vitro cytotoxicity demonstrated that glaucolide 2 and hirsutinolide 4 were toxic to HeLa cells. Compounds 1/3 and 4 were also genotoxic in an in vitro comet assay. Fresh leaves of Vernonia scorpioides are widely used in Brazil to treat a variety of skin disorders. Previous in vivo studies with extracts of this species had also demonstrated a high antitumor potential. This paper reports isolation of four sesquiterpene lactones (hirsutinolides and glaucolides), together with diacetylpiptocarphol, 8-acetyl-13-etoxypiptocarphol, luteolin, apigenin, and ethyl caffeate from fresh leaves and flowers of Vernonia scorpioides. The hypothesis that hirsutinolide 3 is formed during extraction was verified theoretically using Density Functional Theory. The effects of isolated compounds on in vitro tumor cells were investigated, as well as their genotoxicity by means of an in vitro comet assay. The results indicate that glaucolide 2 and hirsutinolide 4 are toxic to HeLa cells. These compounds were genotoxic in vitro, a property that appears to be related to the presence of their epoxy groups, which has been a more reliable indication of toxicity than substitution on C-13 or the presence of α,β-unsaturated keto-groups. These results need to be replicated in vivo in order to ascertain their toxicity.