Ent-Clerodane Diterpenes from the Bark of Croton oligandrus Pierre ex Hutch. and Assessment of Their Cytotoxicity against Human Cancer Cell Lines

Abstract

New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1–10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1–10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate levels of activity against both A549 and MCF7 cells with 1 being the most active with IC50 values of 63.8 ± 13.8 and 136.2 ± 22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC50 = 128.6 ± 31.0 and 111.2 ± 2.9 µM, respectively).

Four new neo-clerodane diterpenes from the stem bark of Croton oligandrus

“…Their FTIR spectrum showed absorption bands of hydroxy (3465 cm -1 ), ɤ-lactone (1775 cm -1 ), α, β-unsaturated lactone (1712 cm -1 ) and olefinic (1670 cm -1 ) groups. Their 1 H and 13 C NMR data rather similar to those of clerodanes crotonolins A and B (1-2), previously isolated from the same plant (Guetchueng et al, 2018) suggested that these compounds were structurally close. Complete assignment of rings A and B and their respective substituents could be achieved easily by comparison of the observed chemical shifts of 3 and 4 with those of crotonolins A and B (1-2).…”

“…Reversed-phase HPLC separation of the methanolic extract of C. oligandrus yielded, in addition to the previously reported compounds (Guetchueng et al, 2018), four new neoclerodanes, named crotonolins C-F (3-6) along with the known clerodane crotonzambefuran A (7) (Ngadjui et al, 2002), the abietanes 7-β-hydroxydehydroabietic acid (8) and 7oxodehydroabietic acid (9) (Tanaka et al, 1997) and ferulic acid (10) (Nguyen et al, 2004) ( Figure 1). The known compounds (7-10) were identified by comparison of their spectroscopic data with their corresponding available data in the literature.…”

“…In Cameroon, it is found in the Central, Southern and Western regions and is used traditionally as a remedy for the treatment of anaemia, pneumonia and splenomegaly (Aubreville, 1983;Jiofack et al, 2009;Betti et al, 2013). In our previous investigation (Guetchueng et al, 2018), we reported five clerodanes: 12-epi-megalocarpoloide D, crotocorylifuran, crotonolins A and B and megalocarpoidolide D along with two triterpenes, acetyl aleuritolic acid and lupeol and three phenolic compounds, cluytyl ferulate, hexacosanoyl ferulate and vanillin. In continuation of our study on the diterpenoids of C. oligandrus, we have investigated the minor constituents of the plants and characterised four new neo-clerodanes, for which we have given the trivial name crotonolins C-F (3-6).…”

Chemical Constituents from Croton Species and Their Biological Activities

“…sylvaticus [ 12 ] and the roots of C. limae [ 13 ], respectively. Eight new clerodane diterpenoids with butenolide at C-9 ( 2 , 3 , 5 , 13 , 14 , 75 , 91 , 92 ) were obtained from three Croton species ( C. crassifolius , C. glabellus , and C. oligandrus ) [ 14 , 15 , 16 , 17 , 18 ]. Furan-clerodane diterpenoids are abundant in Croton species, and 82 new ones were isolated from different Croton species.…”

Justicialosides A and B, two new flavone glycosides from the leaves of Ruspolia hypocrateriformis (Vahl) Milne-Redh. (Acanthaceae)

“…properties (Agbor et al, 2014). As a part of our continuing study on the secondary metabolites of Cameroonian medicinal plants (Wansi et al, 2016;Guetchueng et al, 2017Guetchueng et al, , 2018aGuetchueng et al, , 2018b, we have undertaken the phytochemical investigation of Ruspolia hypocrateriformis. The present work describes the isolation and identification of two new flavone glycosides (1 and 2) from the leaves of this plant (Figure 1).…”