Analysis of Abietane-Type Diterpenoids from Baltic Amber Samples

Abstract

An urgent need exists for novel therapeutics to combat antibiotic-resistant microorganisms, but identification of new drug scaffolds for this purpose remains a challenge. Fossilized material is an emerging source of new chemical matter for drug development. Variations in metabolites produced by extinct species, as well as biotransformations occurring during fossilization, may yield new starting points for therapeutics residing in underexplored chemical space. A promising source of such paleopharmaceuticals is Baltic amber, a fossilized plant resin chiefly produced by extinct pines of the family Sciadopityaceae, and found in the Baltic countries of Lithuania, Latvia and Estonia. Amber has found use in Baltic ethnopharmacology for centuries; however, a systematic and quantitative identification of amber’s bioactive constituents is yet to be reported. Here we present optimized extraction protocols and preliminary GC-MS analyses of Baltic amber samples collected from central Lithuania, as well as comparative analyses of an extant Sciadopitys species: S. verticillata, the Japanese umbrella pine. These experiments revealed the presence of a wide variety of abietane-type diterpenoids unique to the fossilized material, which is of interest given the reported antibacterial, antitumor and antifungal potencies of abietates and related analogs. Three abietates were subsequently confirmed to be selectively active against methicillin-resistant Staphylococcus aureus. Our results support the prioritization of novel abietanes in anti-infective drug design campaigns, and also point to fossilized material as an untapped source of previously uninvestigated natural product-based therapeutic analogs.