Effect of goniothalamin on the development of Ehrlich solid tumor in mice.

In this work the antiproliferative activity of goniothalamin (1), both in racemic and in its enantiomeric pure forms, in a solid tumor experimental model using laboratory animals is described. The antiedematogenic activity displayed by racemic 1 in the carrageenan edema model in mice together with the reduction of Ehrlich solid tumor model suggest a relationship between anticancer and antiinflammatory activities with the antiinflammatory activity favoring the antiproliferative activity itself.

Asymmetric total synthesis and antiproliferative activity of goniothalamin oxide isomers.

Goniothalamin oxide (1) is a styryl lactone which was isolated from bark and leaves of several Goniothalamus species. This natural product has some interesting biological properties such as larvicidal and tripanocidal activities. However, no studies on the antiproliferative profile of goniothalamin oxide (1) and its stereoisomers have been reported yet. Here, goniothalamin epoxide (1), isogoniothalamin epoxide (2) and their enantiomers were prepared via epoxidation of (R)-and (S)-goniothalamin (4). A 3:2 molar ratio in favor of goniothalamin oxide (1) and ent-1 was observed from (R)- and (S)-4, respectively, when 3-chloroperbenzoic acid (mCPBA) was employed while an increase to 6:1 molar ratio was achieved with (S,S)-Jacobsen's catalyst. Antiproliferative activity of these epoxides revealed that ent-isogoniothalamin oxide (ent-2) was the most active against the eight cancer cell lines studied. These results indicate that 6S, 7R and 8R absolute configurations are beneficial for the activity of these epoxides.

Trypanocidal activity of 5,6-dihydropyran-2-ones against free trypomastigotes forms of Trypanosoma cruzi.

Sixteen 5,6-dihydro-2H-pyran-2-ones were evaluated in in vitro assay against trypomastigotes forms of Trypanosoma cruzi, the causative agent of Chagas' disease. A structure-activity relationship study (SAR) allowed us to establish the relevant structural features for the trypanocidal activity of goniothalamin analogues against T. cruzi. In fact, non-natural form of goniothalamin (ent-1) was threefold more potent than the natural one (1). In addition, we have identified analogues 9 and 10 (both displaying S configuration) as the highest potent compounds against T. cruzi with IC50=0.12 and 0.09 mM (IC50 value for crystal violet was 0.08 mM) whereas significantly lower toxicities were observed when these compounds were evaluated under LLC-MK2 lineage cells (1.38 and 4.89 mM, respectively). In addition, epoxides derivatives 12 and ent-12 were shown to be more potent than the corresponding stereoisomers 2 and ent-2 and non-natural argentilactone (ent-3, IC50=0.47 mM) was twofold more potent than natural argentilactone (3, IC50=0.94 mM).