Natural compounds obtained from plants have always held great potential for drug discovery and, as such, have drawn the attention of researchers as novel antifungal molecules that can be effective against fungal resistance. The antifungal activity of sesquiterpene lactones has been extensively investigated against various fungal strains, but there is limited data on their antifungal activity against Candida species. Sesquiterpene lactones are abundant in the Asteraceae family, and 90% of identified sesquiterpene lactones have been isolated from members of this family. Three extracts obtained from the aerial parts of Centaurea salicifolia var. salicifolia , which had not been investigated prior to this study, were tested for their antifungal activity against Candida albicans (ATCC 90028), C. dubliniensis (NCPF 3949a), C. auris (NCPF 8977), C. inconspicua (NCPF 8523), and C. krusei (ATCC 6258) and exhibited minimum inhibitory concentration (MIC) values ranging between 6.25 μg/mL and 12.5 μg/mL. Due to its rich sesquiterpene lactone content, isolation studies conducted on a dichloromethane maceration extract (CsDCM-M) yielded cynaropicrin (SL1), vahlenin (SL2), maximolide (SL3), pectolinaringenin (F1), centaureidin (F2), and axillarin (F3). The isolation of vahlenin from plants has been reported in only two studies, published in 1974 and 1978; thus, the present work constitutes the first documented isolation of vahlenin since the 1970s. Relative stereochemistry elucidation along with the 2D-NMR (COSY, HSQC, HMBC, and NOESY) data for vahlenin is given for the first time. Antifungal tests against the abovementioned Candida strains were also performed using all of the isolated compounds, and they exhibited promising MIC values between 12.5 μg/mL and 50 μg/mL. This is the first report on the antifungal activity of vahlenin and maximolide against C. auris , C. inconspicua , and C. dubliniensis .

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Twenty-nine compounds were isolated from the aerial parts of the Greek plant C. zuccariniana DC. The structures of the isolated compounds were established by means of NMR- ((1) H,(1) H-COSY, (1) H,(13) C-HSQC, HMBC, NOESY, and ROESY) and mass-spectral analyses. These compounds comprise 13 sesquiterpene lactones, 14 flavonoids, two lignans, and one simple lactone. Among the isolated sesquiterpene lactones, three are new, namely one heliangolide, (1E,4Z)-15-hydroxy-8α-O-(4'-acetoxy-3'-hydroxy-2'-methylidenebutanoyl)-6βH,7αH-germacra-1,4,11(13)-trien-6,12-olide; and two eudesmanolides, 8α-(4',5'-diacetoxyangeloyl)sonchucarpolide and one unusual eudesmanolide with an oxygenated bridge linking C(1) and C(4), named zuccarinin. The main sesquiterpene lactones were malacitenolide, cnicin, and 4'-O-acetylcnicin. These results are in agreement with those obtained from the previously studied Greek Centaurea sp. belonging to the section Acrolophus (Cass.) DC.; this finding could be of chemotaxonomic significance for the genus Centaurea. The in vitro antimicrobial activities of the isolated new sesquiterpene lactones were against eight bacteria and eight fungal species. A 96-well microbioassay procedure for fast and easy evaluation of antibacterial and antifungal activities was applied to compare these compounds with commercial antibiotic and fungicide standards, and with previously isolated analogous sesquiterpene lactones tested by the same bioassay. All of the compounds tested showed moderate antibacterial, but significant antifungal activities; the present results corroborate with previous data, indicating that these types of compounds exhibit low or moderate antibacterial, but potent antifungal activities. The unusual eudesmanolide zuccarinin proved to be the most potent among the present tested sesquiterpene lactones, as well as among all previously tested eudesmanolides isolated from Greek Centaurea sp.

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