Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Oxygenated C 17 polyacetylene metabolites from Algerian Eryngium tricuspidatum L. roots: Structure and biological activity A. Djebara a,b , M.L. Ciavatta a, ⁎ , V. Mathieu c,d , M. Colin c , F. Bitam e , M. Carbone a , M. Gavagnin a a Consiglio Nazionale delle Ricerche (CNR), Istituto di Chimica Biomolecolare (ICB), Via Campi Flegrei, 34, 80078 Pozzuoli, Napoli, Italy b Laboratoire de Chimie et Chimie de l'Environment, Faculté des Sciences de la Matiere, Departament de Chimie, Universitè de Batna-1, 05000, Algeria c Department of Pharmacotherapy and Pharmaceutics, Faculty of Pharmacy, ULB, Campus de la Plaine, Blvd du Triomphe, 1050 Brussels, Belgium d U-CRC, ULB Cancer Research Center, ULB, route de Lennik, 808, 1070 Brussels, Belgium e Faculté de Médecine, Département de Pharmacie, Université de Batna-2, 05000, Algeria ARTICLEINFO Keywords: Eryngium tricuspidatum: Apiaceae Polyacetylenes Falcarindiol Antiproliferative activity ABSTRACT The secondary metabolite pattern of Eryngium tricuspidatum has been found to be dominated by C 17 acetylene oxylipins, according to the chemistry reported in the literature for the genus Eryngium. Two new oxylipins, 11- acetoxy-falcarindiol (4) and 1,2-dihydro-11-acetoxy-falcarindiol (5) have been isolated, along with main related polyacetylenes 1–3 and the already known monoterpene aldehydes 6–10, from the petroleum ether extract of roots. The structure and the absolute confguration of compounds 4 and 5 have been determined by spectro- scopic methods as well as by comparison with related known compounds. Polyacetylenes 1–4 inhibited sig- nifcantly the in vitro growth of a series of cancer cell lines, ranging from 0.3 to 29 μM, whereas 5 was inactive. 1. Introduction The genus Eryngium is the largest and arguably the most tax- onomically complex genus of Apiaceae family (Umbelliferae) [1]. The genus comprises approximately 300 species throughout the world in- cluding species cultivated as ornamental, vegetable, or medicinal crops for folk uses. Eryngium tricuspidatum L. (syn. Eryngium zanonii) that is native to North Africa, Malta, Sicily, and Sardinia, is commonly known as sea holly and is characterized by dark blue fowers appearing in Summer and silver foliage. The perennials reach heights of 50 to 150 cm and produce achenes whereas the leaves are arranged opposite to one another and are pinnate. The plant grows in sunny sites and can withstand sandy and drought-prone soils as well as temperatures down to −12 °C [2]. E. tricuspidatum is one of seven Eryngium species endemic in Algeria, mainly distributed in the northern regions of the country [3]. Analo- gous with other plants of this genus, E. tricuspidatum (vernacular name: M'ghizla) is used by local populations as folk remedy for the treatment of various disorders. In particular, the decocotion of its roots is efective against poisoning and constipation [4], and also to relieve labor pain [5]. Several studies on the chemistry and pharmacological activities of plants of Eryngium genus have been reported to date in the literature [6]. A large array of chemicals, that are terpenoids, polyacetylenes, steroids, triterpenoid saponins, favonoids, and coumarins, displaying a variety of biological properties such as antitumour, antibacterial, an- timicrobial, antifungal, and phototoxic activities have been described from distinct species of Eryngium genus [6]. The phytochemical con- stituents of E. tricuspidatum have been investigated in recent years with regards to the aerial parts whereas, to the best of our knowledge, no chemical analysis of the roots of the plant has been reported to date. In particular, two papers described the chemical composition and biolo- gical activity, including antibacterial, antioxidant, tyrosinase in- hibitory, and antifungal properties, of the essential oil [7] and phenolic glycoside [8] mixtures obtained from the extracts of the aerial parts of E. tricuspidatum collections from northwestern and northeastern Al- geria, respectively. In continuing our phytochemical studies on Algerian plants [9–12], we have investigated the content of the petroleum ether extract of the roots of E. tricuspidatum collected in North Algeria. This study has re- vealed a secondary metabolite pattern dominated by oxygenated C 17 polyacetylenes (compounds 1–5) and monoterpenoid aldehydes (com- pounds 6–9). Compounds 4 and 5 were new enynols structurally related to co-occurring (3S,8S)-falcarindiol (3). Falcarindiol-3,8-diacetate (1) was never reported as naturally occurring metabolite. The in vitro growth inhibitory properties of polyacelylenes 1–5 on a panel of cancer https://doi.org/10.1016/j.ftote.2019.104355 Received 22 July 2019; Received in revised form 6 September 2019; Accepted 10 September 2019 ⁎ Corresponding author. E-mail addresses: lciavatta@icb.cnr.it (M.L. Ciavatta), Veronique.Mathieu@ulb.ac.be (V. Mathieu), Margaux.Colin@ulb.ac.be (M. Colin), f.bitam@univ-batna2.dz (F. Bitam), mcarbone@icb.cnr.it (M. Carbone), mgavagnin@icb.cnr.it (M. Gavagnin). Fitoterapia 138 (2019) 104355 Available online 11 September 2019 0367-326X/ © 2019 Elsevier B.V. All rights reserved. T