No abstract

This paper presents a review on kaurane diterpenes and their glycoside derivatives, covering aspects of their occurrence, biological activities and the synthesis of these natural products and their analogues. First, it shows and classifies diterpenes, in accordance with the already established structural criteria in the literature. Then, kaurane diterpenes are presented, focusing on their chemical structures, occurrence in the plant kingdom and their main, recently described, biological activities. Moreover, the most significant works, published between 1964 and November 2006, which describe the total synthesis or structural transformations of some kaurane diterpenes, including either semisynthetic and/or microbiological methodologies, are consisely reviewed. At this point, some general considerations on glycosides are introduced, and kaurane glycosides are presented and discussed on the basis of their toxic importance and occurrence in the plant kingdom, having focused on related aspects of their biological activities and the relationships between these activities and the structural factors of their molecules. Finally, the principal methods of glycosidation by enzymatic and chemical processes are both presented, and a few papers on the synthesis of kaurane glycosides are succinctly discussed. Molecules 2007, 12 456

aThe chemical composition and bioactive properties of two plants (Calendula officinalis L. and Mentha cervina L.) were studied. Their nutritional value revealed a high content of carbohydrates and low fat levels, and very similar energy values. However, they presented different profiles in phenolic compounds and fatty acids; C. officinalis presented mainly glycosylated flavonols and saturated fatty acids, while M. cervina presented mainly caffeoyl derivatives and polyunsaturated fatty acids. M. cervina showed the highest concentration of phenolic compounds while C. officinalis presented higher amounts of sugars, organic acids and tocopherols. The highest antioxidant and cytotoxic activities were obtained for the hydromethanolic extract of M. cervina, which presented the lowest values of EC 50 and exhibited cytotoxicity against the four tumor cell lines tested. Infusions showed no cytotoxicity for the tumor cell lines, and none of the extracts showed toxicity against non-tumor cells. This study contributes to expand the knowledge on both natural sources and therefore their use.

Several series of nonlactonic podophyllic aldehyde analogues were prepared and evaluated against several human tumor cell lines. They had different combinations of aldehyde, imine, amine, ester, and amide functions at C-9 and C-9' of the cyclolignan skeleton. All the compounds synthesized showed cytotoxicity levels in the microM range and below. Within the new series tested, compounds having an aldehyde or imine at C-9 and an ester at C-9' were the most potent, with GI(50) values in the nM range, some of them being several times more potent against HT-29 and A-549 carcinoma than against MB-231 melanoma cells. Cell cycle studies and analysis of the microtubule-disrupting capacity have demonstrated the existence of two different mechanisms of cell death induction for compounds with closely related structures.