Synthesis of novel podocarpa-8,11,13-triene-7- and 13-nitriles and evaluation of their anti-inflammatory and cytotoxic activity

A series of novel podocarpa-8,11,13-triene-7- and 13-nitriles were prepared from the naturally occurring labdane diterpenoid (+)-manool, using podocarp-8(14)-en-13-one and 13-methoxypodocarpa-8,11,13-trien-7-one as key intermediates and TMSCN and acetonitrile as source of the nitrile. The synthesised compounds were screened for cytotoxicity against mouse macrophage cell line (RAW 264.7), human colon adenocarcinoma cell lines (HT-29) and human prostate adenocarcinoma cell lines (PC3) and for anti-inflammatory, as measured by the inhibition of nitric oxide (NO) production by RAW cells. 7-Oxopodocarpa-8,11,13-triene-13-nitrile exhibited significant inhibition of NO production (IC50 = 6 mu M) and was not cytotoxic.