Contents lists available at ScienceDirect Bioorganic Chemistry journal homepage: www.elsevier.com/locate/bioorg Hopane-type triterpenes from Cnidoscolus spinosus and their bioactivities Fabiola A. López-Huerta a , Antonio Nieto-Camacho a , Félix Morales-Flores a , Simón Hernández-Ortega a , María Isabel Chávez a , Carlos A. Méndez Cuesta b , Ignacio Martínez c , Bertha Espinoza c , Francisco J. Espinosa-García d , Guillermo Delgado a, ⁎ a Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán 04510, Ciudad de México, Mexico b Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Calzada del Hueso 1100, Ciudad de México 04960, Mexico c Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Coyoacán 04510, Ciudad de México, Mexico d Instituto de Investigaciones en Ecosistemas y Sustentabilidad, Universidad Nacional Autónoma de México, Ex Hacienda de San José de la Huerta 58190, Morelia, Mexico ARTICLEINFO Keywords: Cnidoscolus spinosus Triterpenes Hopanes Anti-infammation 3β-acetoxy-hop-22(29)-ene ABSTRACT Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3β-acetoxy-hop-22(29)-ene (1), frst reported here as natural product, together with 3- oxo-hop-22(29)-ene (2), and 3β-hydroxy-hop-22(29)-ene (3). β-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confrmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-infammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1–3 did not show cytotoxic activity, compound 1 displayed an important inhibitory efect in the mouse ear induced infammation assay, and signifcantly inhibited the yeast α- glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-infammatory properties. 1. Introduction The genus Cnidoscolus belongs to the Euphorbiaceae family and is endemic to the American continent. Plants of this genus are herbs, shrubs or small trees characterized by the presence of urticating tri- chomes throughout the plant [1]. The Plant List data base includes ca. 90 accepted names for Cnidoscolus species [2], and a signifcant number of these are endemic of Mexico, distributed in tropical and subtropical regions, mainly in low deciduous forest and xerophilous scrub [3,4]. Preparations using the aerial parts of some species such as C. aconiti- folius [5,6], C. chayamansa [7–9], C. quercifolius [10] and C. multilobus [11] have been reported in traditional medicine for the treatment of diabetes, fu, anti-infammatory related diseases, stomach infections, and rheumatism [12]. Previous chemical investigations on this genus established the presence of favonoids [13], triterpenes [14], diterpenes [15], coumarins [16] and steroids [5]. C. spinosus [17] is an endemic species to Mexico and is mainly found in the Pacifc coast in the states of Nayarit, Jalisco, Colima and Guerrero [18,19]. This plant is abundant in places with strong environmental disturbance [20], and up to date, there is no record of its use in traditional medicine. Aiming to expand the chemical and biological knowledge of this genus and considering that only the presence of favonoids has been reported from C. spinosus [17], the aerial parts of this plant were investigated. Herein, we report the isolation and structural determination of four pentacyclic tri- terpenes, including one new hopane (whose skeleton is not frequent in plants), and three phytosterols. Cytotoxic, anti-infammatory, in- hibitory activity toward α-glucosidase (from yeast and rat), and anti- parasitic (against strains of Trypanosoma cruzi, T. rangeli and Leishmania mexicana) properties of the isolated hopanes have been evaluated. 2. Materials and methods 2.1. General experimental procedures Melting points were determined on a Fisher Johns apparatus and are uncorrected. Optical rotations were measured using a Perkin Elmer 343 polarimeter (hexane, c in g/100 mL). UV spectra were taken on a Shimadzu UV–visible recording spectrophotometer. IR spectra were recorded on a FT-IR Bruker Tensor 750. NMR spectra were recorded in either a Bruker Avance III or a Bruker Ascend 700 spectrometer, using https://doi.org/10.1016/j.bioorg.2020.103919 Received 13 December 2019; Received in revised form 5 April 2020; Accepted 6 May 2020 ⁎ Corresponding author. E-mail address: delgado@unam.mx (G. Delgado). Bioorganic Chemistry 100 (2020) 103919 Available online 11 May 2020 0045-2068/ © 2020 Published by Elsevier Inc. T