Cytotoxic activity of (S)-goniothalamin and analogues against human cancer cells

Synthesis and leishmanicidal activity of cinnamic acid esters: structure–activity relationship

“…The smaller the alkyl chains the higher the selectivity index (5, 6 vs 7-12); the degree of oxygenation is essential for activity, primarily in positions 2, 3 and 4 (12 vs 13-17); hydroxyl groups increase both the activity and cytotoxicity (9 vs 18); The importance of the double bond is not conclusive since the compounds were inactive, which can be related to the degree of oxygenation (16 vs 17). However, if the action mechanism involves a Michael addition for nucleophilic amino acid residues, this would be crucial for the activity as has been reported for other α,β-unsaturated compounds such as lactones, chalcones and cumarins (De Fatima et al, 2006;Buck et al, 2003). The leishmanicidal activity against the intracellular forms of Leishmania parasites was also measured for all compounds.…”

The Medicinal Value of Biodiversity: New Hits to Fight Cancer

“…Recently, we have described not only the synthesis, but also the antiproliferative activities of both (R)-and (S)-goniothalamin. Interestingly, we found that (S)-goniothalamin (IC 50 = 6.4 μM) was 1,600-fold more potent than (R)-goniothalamin (IC 50 = 4.0 nM) in renal 786-0 cancer cells (de Fátima et al, 2006b). As reported for (R)-goniothalamin (Pihie et al, 1998;de Fátima et al, 2005 and cited references), we demonstrated that (S)-goniothalamin exhibited pronounced selectivity for cancer cells, while presenting minor cytotoxicity against non-tumor cells (de Fátima et al, unpublished results).…”

“…(5) (6)( 7) We found that (S)-goniothalamin was 4,750-and 5,200-fold more potent in inhibiting proliferation of kidney cancer cells (786-0) than analogues 1 and 3, respectively (de Fátima et al, 2006b). Remarkably, analogue 4 with a cyclohexyl substituent conserved the same cytotoxic activity as (S)-goniothalamin against renal 786-0 cancer cells, being active at the nanomolar level (IC 50 = 5 nM).…”

“…Although the biological activities exhibited by the natural form of goniothalamin (6R absolute configuration) have been widely investigated, no studies about the biological activities of (S)-goniothalamin (Fig. 2) were reported up to 2005(de Fátima et al, 2006bKasaplar et al, 2009). Recently, we have described not only the synthesis, but also the antiproliferative activities of both (R)-and (S)-goniothalamin.…”

Antiprotozoal Activity of &#945,&#946-Unsaturated &#948-Lactones: Promising Compounds for the Development of New Therapeutic Alternatives

“…The results shows that the α,β-unsaturated-δ-lactone moiety is essential for biological activity. This is due to the fact that this unit is an excellent potential Michael acceptor for nucleophilic amino acid residues (cysteine, lysine, serine or threonine) and N7 of guanine present in biomolecules of the natural receptors interacting with these compounds [47,48]. Several compounds showed high antiprotozoal activity, but cytotoxic properties were also observed.…”