title: Cyparissins A and B, jatrophane diterpenes from Euphorbia cyparissias as Pgp inhibitors and cytotoxic agents against ovarian cancer cell lines.
abstract: From the whole plant of Euphorbia cyparissias, two new diterpenes based on jatrophane skeleton, named cyparissins A and B (1 and 2) were isolated. Their chemical structures were established through a combination of nuclear magnetic resonance spectroscopy and mass spectrometric methods. The new cyparissins A and B were tested to evaluate their ability to inhibit P-glycoprotein-mediated multidrug resistance and their cytotoxic activity against A2780 human ovarian cancer cells, both WT and ADR. Compounds 1 and 2 showed moderate inhibitory effects on P-glycoprotein while showing a significant concentration-depending cytotoxic activity for both cancer cell lines. These isolated compounds are based on a new chemical structure that expands the knowledge base for this class of bioactive metabolites.
authors.affiliation: Dipartimento di Agraria, Università di Napoli Federico II, Portici, Napoli, Italy. Electronic address: lanzotti@unina.it.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lanzotti
authors.affiliation: Sanford-Burnham Institute for Medical Research, San Diego, CA, United States.
authors.forename: Elisa
authors.initials: E
authors.lastname: Barile
authors.affiliation: Dipartimento di Ostetricia e Ginecologia, Università Cattolica del Sacro Cuore, Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Danbury Hospital Research Institute, Danbury, CT, United States.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferlini
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D005260:Female; D006801:Humans; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C000601748:cyparissin A; C000601749:cyparissin B; C530345:jatrophane
keywords: A2780 WT and ADR; Cyparissin; Cytotoxic activity; Euphorbia cyparissias L; Jatrophane diterpenes; P-gp inhibition