Cytotoxic Clerodane Diterpenoids from the Leaves of Casearia grewiifolia

Abstract

Two new clerodane diterpenoids (1 and 2) and the known compound caseanigrescen D (3) were isolated from the leaves of Casearia grewiifolia by bioassay-guided fractionation. Their structures were determined by analyses of MS and 2D NMR data. The absolute configurations of 1 and 3 were established by analysis of X-ray diffraction data. Compounds 1-3 were evaluated for their cytotoxicity against four cancer cell lines, KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). Caseagrewifolin B (2) had inhibitory activity against KB and HepG-2 cell lines with IC50 values of 6.2 to 7.0 μM, respectively. When tested against the normal cells (NIH/3T3), caseagrewifolin B (2) exhibited a significant selective inhibition against cancer cells in comparison with the normal cells. Caseanigrescen D (3) was cytotoxic against four cancer cell lines; however it had no selective inhibition compared with normal cells.

Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells

“…In fact, the flavanone dorsmanin F [24] previously displayed IC 50 values below 10 μM towards leukemia CCRF-CEM cells and breast adenocarcinoma MDA-MB-231 cells; however, this compound also had IC 50 values above 10 μM in several other cancer cell line when tested in similar experimental conditions [24]. The three clerodane type diterpenoids ( 7–9 ) were not active against the tested cancer cell lines within the tested concentration ranges; nevertheless, the cytoxicity of clerodane diterpenoids was demonstrated [7], [8], [9], [10] where, caseariagraveolin isolated from Casearia graveolens showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC 50 values of 2.48 and 6.63 μM [27]. Other strong cytotoxic clerodane diterpene include casearin J [9] and caseagrewifolin B [8].…”

“…The three clerodane type diterpenoids ( 7–9 ) were not active against the tested cancer cell lines within the tested concentration ranges; nevertheless, the cytoxicity of clerodane diterpenoids was demonstrated [7], [8], [9], [10] where, caseariagraveolin isolated from Casearia graveolens showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC 50 values of 2.48 and 6.63 μM [27]. Other strong cytotoxic clerodane diterpene include casearin J [9] and caseagrewifolin B [8]. The cytotoxicity of trachylobane diterpenoids has also been reported and the reported effects of compounds 10 and 11 were in consistence with the previous studies [28] where, ent-trachyloban-3beta-ol, had cytotoxic activity against human cervix carcinoma cells, displaying IC 50 value of 7.3 μM on HeLa cells [28].…”

“…Diterpenoids are terpenoids having two terpene units (C20). Phenolic compounds such as chalcone, flavanones as well as diterpenoids including clerodane and trachylobane types possess various pharmacological properties including cytotoxic effects in various cancer cell lines [7], [8], [9], [10], [11]. In our continuous search of antiproliferative molecules to fight cancers, the present study was undertook to investigate the cytotoxicity of eleven compounds including six phenolics amongst which were four chalcones and two flavanones as well as five terpenoids including three clerodane type and two trachylobane type diterpenoids previously isolated from Kenyan medicinal plants.…”

Diterpenes and Their Derivatives as Potential Anticancer Agents

“…Moreover, the diterpenes cembranoids (Cheng et al , ), andrographolide and its analogues (Mishra et al , ), 11α, 12α‐epoxyleukamenin E (Ye et al , ; Valdés et al , ), jesridonin (Wang et al , ), carnosic acid, carnosol, rosmanol (Petiwala and Johnson, ), clerodane diterpenoids (Nguyen et al , ), rhizovarins A‐F (Gao et al , ) and so on, are also evident to exert an antitumoral effect on a number of cancer cell lines as well as other biological test systems. Some important anticancer diterpenes have been shown in Fig.…”

Corymbulosins I–W, Cytotoxic Clerodane Diterpenes from the Bark of Laetia corymbulosa

“…1 In particular, Zuelania and Casearia genera typically yield such diterpenes, including esculentin A and zuelaguidins A−D and F from Z. guidonia , 2 caseanigrescens A−D from C. nigrescens , 3 argutins A−H from C. arguta , 4 caseamembrins A−U from C. membranacea , 5–9 caseabalansin A−G and balanspenes A−H from C. balansae , 10,11 and caseagrewiifolins A and B from C. grewiifolia . 12 In these compounds, the tricyclic system normally is formed from a cis-fused decalin with a disubstituted tetrahydrofuran connected at C-4−C-5. Further characteristic features are two trans-configured methyls at C-8 and C-9 and a 3-methylenepent-4-en-1-yl side chain at C-9.…”