Isolation and structure elucidation of secondary metabolites of two Greek endemic Inula species. Biological activities

Abstract

In the framework of phytochemical studies on Greek endemic Inula species, Inula candida subsp. candida and Inula candida subsp. decalvans have been analyzed. The aerial parts were extracted with increasing polarity solvents and sixteen secondary metabolites from I. candida subsp. candida and eight from I. candida subsp. decalvans were isolated. From I. candida subsp. decalvans a sesquiterpene lactone (3aS,8aR)-6-methyl-3-methylidene-7-(3-oxobutyl)-3a,4,5,8a-tetrahydro-2H-cyclohepta[b]furan-2,8(3H)dione (1), was determined as a new natural product, additionally to five known triterpenes: β-amyrin (2), dammaradienol (3), dammaradienyl acetate (4), epifriedelanol (5), stigmasterol (6) and two known lactones: inusoniolide (7) and tomentosine (8). The chemical investigation of I. candida subsp. candida resulted in the isolation of ten known triterpenes: β-amyrin (2), stigmasterol (6), β-sitosterol (9), α-amyrone (10), α-amyrin (11), friedelin (12), lupenone (13), 3β-acetoxy-24-hydroxydammara-20,25-diene (14), 3β-acetoxy-25-hydroxydammara-20,23-diene (15), 3β-acetoxy-24-oxo-dammara-20,25-diene (16), as well as five lactones: inusoniolide (7), 4-O-dihydroinusoniolide (17), 9β-(3-hydroxyisovaleryloxy) parthenolide (18), 9β-hydroxyparthenolide (19), 9β-(3-hydroxy-2-methylbutyryloxy) parthenolide (20), together with the phenolic aldehyde: vanillin (21). The crude extracts and the isolated compounds were also evaluated for their antimicrobial activity against a panel of selected human pathogenic bacteria and fungi showing that the new lactone (1) and 9β-hydroxyparthenolide (19) showed the strongest activity against the tested bacteria (MIC 3•10−2–5•10−1 μg/ml), while (1) and tomentosin (8) appeared as the most active against the assayed fungi (MIC 2,5•10−2–12•10−2 μg/ml). The antiproliferative effect for the new lactone was also evaluated in vitro against the human non-small-cell bronchopulmonary carcinoma cell line NSCLC-N6 and the epidermoid lung cancer cell line A549.