A chemotaxonomic study of endemic species of genus Tanacetum from the Canary Islands Jorge Triana a , José Luis Eiroa a,⇑ , Manuel Morales a , Francisco J. Pérez a , Ignacio Brouard b , María Teresa Marrero c , Sara Estévez c , José Quintana c , Francisco Estévez c , Quírico A. Castillo d , Francisco León b,e,⇑ a Departamento de Química, Unidad Asociada al CSIC, Universidad de Las Palmas de Gran Canaria, Campus de Tafira, 35017 Las Palmas de Gran Canaria, Canary Islands, Spain b Instituto de Productos Naturales y Agrobiología-Consejo Superior de Investigaciones Científicas (CSIC), Avda. Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain c Departamento de Bioquímica, Universidad de Las Palmas de Gran Canaria, Instituto Canario de Investigación del Cáncer, Plaza Dr. Pasteur s/n, 35016 Las Palmas de Gran Canaria, Canary Islands, Spain d Escuela de Química e Instituto de Química, Universidad Autónoma de Santo Domingo, Facultad de Ciencias, Ciudad Universitaria, Santo Domingo D.N., Dominican Republic e Medicinal Chemistry Department, School of Pharmacy, University of Mississippi, MS 38677, USA article info Article history: Received 19 November 2012 Received in revised form 26 April 2013 Accepted 29 April 2013 Available online 25 May 2013 Keywords: Tanacetum oshanahanii T. ptarmiciflorum T. ferulaceum var. latipinnum Asteraceae Anthemidinae Chemotaxonomy Sesquiterpene lactones Leukemia HL-60 and U937cell lines abstract Aerial parts of Tanacetum oshanahanii collected at ‘‘Jardín Canario Viera y Clavijo’’, Tanacetum ptarmiciflo- rum collected at Los Moriscos (Tejeda), and Tanacetum ferulaceum var. latipinnum collected at Anden Verde (Agaete) in Gran Canaria, Canary Islands, afforded three sesquiterpenes related to nerolidol and six sesquiterpene lactones whose structures were established on the basis of their spectroscopic data and chemical transformations. In this work we show that this type of sesquiterpene lactones could be used as chemotaxonomic markers. A series of sesquiterpene lactones described in this paper were assessed for cytotoxicity against HL-60 and U937 cancer cell lines. The derivatives 106a and 98a dis- played cytotoxic properties showing IC 50 values between 5 and 11 lM. Furthermore, we demonstrated that these selected sesquiterpene lactones induce apoptotic cell death in human leukemia cells through a mechanism that involves activation of multiple caspases and moreover cell death was found to be asso- ciated with the release of cytochrome c. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction The subtribe Anthemidinae is the second largest in the Ant- hemideae tribe containing the rich genus Tanacetum (154 spp.). While the circumscription of the subtribe as monophyletic is quite clear based on the embryological findings, the generic delimita- tions and the phylogenetic relationship within the subtribe remain unresolved, despite the assessment of Bremer and Humphries (Bre- mer and Humphries, 1993; Funk et al., 2009) that ‘‘there are sev- eral segregate genera and groups of genera, possibly even whole subtribes, which are related to parts of Tanacetum’’ making it a highly paraphyletic genus. Studies based on ITS sequence variation with a number of Tanacetum species included, have shown that the Mediterranean and Southwest Asia representatives of the genus are closely related. To arrive at monophyletic genus Tanacetum around the type species Tanacetum vulgare L., some species will have to be removed and transferred to other genera. Preliminary analyses have already clearly shown that the Canary Islands ende- mic genera Gonospermum and Lugoa (Triana et al., 2010) represent derivatives closely related to the Tanacetum species endemic to this archipelago and, therefore, should be included in a monophy- letic genus Tanacetum (Francisco-Ortega et al., 2001; Oberprieler, 2005; Oberprieler et al., 2007). The sesquiterpene lactones are a very important group of ses- quiterpenoids isolated predominantly from the Asteraceae family. Sesquiterpene lactones appear to have a common biosynthetic ori- gin, and are likely to provide useful chemical characters in the tribe. Germacranolide-type lactones are simple representatives of this group of compounds and may be considered to be the bioge- netic precursors of other skeletal types of lactones (De Kraker et al., 2002). Further ring closures produce eudesmanolides and guaianolides. The occurrence of sesquiterpene lactones is biogenetically especially significant in T. vulgare, because all the sesquiterpene lactones isolated from T. vulgare species possess an a-methylene- c-lactone moiety, and this feature can been claimed to be 0031-9422/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.phytochem.2013.04.015 ⇑ Corresponding authors at: Tel.: +34 922 256847x224; fax: +34 922 260135. E-mail addresses: jeiroa@dqui.ulpgc.es (J.L. Eiroa), jfleon.oyola@gmail.com (F. León). Phytochemistry 92 (2013) 87–104 Contents lists available at SciVerse ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem