Casearin X, Its Degradation Product and Other Clerodane Diterpenes from Leaves of Casearia sylvestris: Evaluation of Cytotoxicity against Normal and Tumor Human Cells

Abstract

An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F. Casearin X degraded to the corresponding dialdehyde when stored in CDCl(3). The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC(50) values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity.

Maternal–fetal safety evaluation of an aqueous extract of Casearia sylvestris leaves in rats

“…One of these studies on hydroethanolic extract of C. sylvestris leaves showed no toxicity after a single (acute) or repeated exposure (28 and 90 days) and indicated that the LD50 (lethal dose for 50% of the population) of this extract was greater than 2000 mg/kg. Other previous studies have also reported low in vivo and in vitro toxicity of C. sylvestris (Basile et al, 1990;Ferreira et al, 2014;Maistro et al, 2004;Santos et al, 2010). However, no study has investigated the effects of this species during critical periods of development, particularly the organogenesis period, which is when the main organs develop.…”

Cytotoxic activity of casearborin c isolated from Casearia corymbosa

“…The genus Casearia includes 180 species [3] and belongs to Salicaceae family. This family is constituted of 54 genera and 1,200 species, composed of trees or bushes of cosmopolitan distribution [4], and considered as source of clerodane-type diterpenes [5][6][7]. In the Yucatan peninsula there are four species of the genus Casearia [8], including Casearia corymbosa Kunth.…”

Metabolism Characterization and Chemical and Plasma Stability of Casearin B and Caseargrewiin F

“…Besides the cytotoxicity against human tumor cell lines [2,3,5,[11][12][13][14][15][16], casearin X and a pool of casearins inhibited tumor growth in mice when orally administered [5]. Casearins promoted cell death via apoptotic pathways in vitro [16] and were selective to tumor cell lines [15]. C. sylvestris leaf extracts and casearin-type diterpenes showed antiulcer activity after oral administration in rats [10,17].…”

“…However, the oral absorption and metabolism processes of the clerodane diterpenes cas B and casg F were never explored. In vitro assays simulating oral administration of casearins J and O generated the respective dialdehydes as main degradation products and metabolites [18], as previously described for casearin X [15].…”

“…The antitumor action of casearin-type diterpenes has been evaluated since the 1980 s [11]. Besides the cytotoxicity against human tumor cell lines [2,3,5,[11][12][13][14][15][16], casearin X and a pool of casearins inhibited tumor growth in mice when orally administered [5]. Casearins promoted cell death via apoptotic pathways in vitro [16] and were selective to tumor cell lines [15].…”