Novel Bioactive Clerodane Diterpenoids from the Leaves and Twigs of Casearia sylvestris

Abstract

Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.

Folk uses and pharmacological properties of Casearia sylvestris: a medicinal review

“…Natives from the Shipibo-Conibo tribe (Peru) utilize bark decoction for flu and chest colds (Hoehne 1939). Certainly, the antimicrobial action against pathogens as fungi (Aspergilus niger, Saccharomyces cerevisiae, Candida albicans, Candida tropicalis) (Carvalho et al 1998, Oberlies et al 2002, Da Silva et al 2008b) and bacteria (Bacillus subtilis, Bacillus cereus, Staphyloccoccus aureus, Enterococcus faecalis, Salmonella enteriditis) (Chiappeta et al 1983, Mosaddik et al 2004, Da Silva et al 2008b) explains the uses to treat wounds, skin ulcerations and diarrhea.…”

“…In view of the fact that the water extract was more efficient in neutralizing hemorrhagic metalloproteinases Carvalho et al 1998, Itokawa et al 1990, Morita et al 1991, Oberlies et al 2002, Wang et al 2009, Ferreira et al 2010, Santos et al 2010 from bothropic venoms than neutralize serina-proteases, it is proposed that this extract may act as a metal natural chelating (Borges et al 2001). Other possibility would be linkage of the active compound, present in the extract, to the enzyme catalytic site which could avoid coupling of the substrate to the enzyme in a covalent or non-covalent interaction way.…”

“…The diacetalic ring is a highly oxygenated structure rarely seen in natural molecules, being a protected dialdehyde (Santos et al 2007). Bioguided fractionation assays have regularly revealed that clerodane diterpenes, predominantly those rich in oxygen atoms, possess antifungal, antibacterial, insecticidal, antifeedant and cytotoxic properties (Morita et al 1991, Merrit and Ley 1992, Oberlies et al 2002, Vieira-Junior et al 2009). …”

“…Twenty eight clerodane diterpenes typical of Casearia were isolated from C. sylvestris: casearins A-X (Carvalho et al 1998, Itokawa et al 1990, Morita et al 1991, Wang et al 2009, Santos et al 2010 and caseargrewiin F (Santos et al 2010), isolated from leaves; casearvestrins A-C, isolated from leaves and branches (Oberlies et al 2002);and rel-19S-acetoxy-18R-butanoyloxy-18,19-epoxy-6S-hidroxy-2R-(2-methylbutanoyloxy) -5S, 8R, 9R, 10S-cleroda-3,13(16),14-triene, isolated from roots (Espíndola et al 2004) (Fig. 1).…”

Efecto in vitro de los terpenos lupeol y casearina G sobre células sanguíneas y tumorales

“…Estudios de citotoxicidad muestran que C. sylvestris presenta un interesante potencial antitumoral debido a la presencia de casearinas 6,7 . Ha sido descrito que el aceite de C. sylvestris presenta citotoxicidad contra las células tumorales HeLa, A-549 y HT-29 y efecto hemolítico sobre eritrocitos de diferentes especies 8 .…”