Plectranthus aliciae: Biological activity of 6,7-dehydroroyleanone and derivatives

Plectranthus genus (Lamiaceae) is known to be rich in bioactive abietane royleanone-type diterpenes, such as the 6,7-dehydroxyroyleanone (1). This abietane royleanone 1 can be isolated from P. madagascariensis (var. aliciae Codd) essential oil and present cytotoxic activity against several cancer cell lines. Moreover, 1 has one hydroxyl group that offers an opportunity for derivatization, which can be strategically explored to increase the cytotoxic potential of lead compound 1. Considering this, the aim of the present work was to explore the obtention of 1, from P. aliciae (Codd) van Jaarsv. & T.J.Edwards., a subspecies of P. madagascariensis. to be further used in the preparation of new ester derivatives with enhanced biological activities. A hydrodistillation using Clevenger equipment was performed on P. aliciae leaves, to afford the essential oil (EO). Royleanone 1 was assessed as the major compound of the EO, by HPLC-DAD. Furthermore, compound 1 was isolated and used as a scaffold for esterification reactions. It was possible to synthesize three new acyl derivatives (2 to 4), with overall good yields (86 - 95 %). Regarding the biological activity screening, all the semi-synthetic derivatives (2-4) improved the antioxidant activity and the cytotoxicity in MCF-7 and NCI-H460 human cancer cell lines, when compared to the parent compound 1. Notably, the new esters (2-4) showed promising anti-inflammatory activities, in a range of 16 to 53 times higher than 1 and surpassed the positive control dexamethasone. Currently, the mechanism of action and safety of the potential anti-inflammatory derivatives are under evaluation.