- Shuso Takeda (Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU) / firstname.lastname@example.org)
1) Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU) , 2) Institute for Materials Chemistry and Engineering, Kyushu University
Stemona alkaloids such as (±)-stemonamine/ (±)-isostemonamine, have a unique structure, possibly coupled with potential biological activities. The establishment of effective total synthesis protocols for stemonamine alkaloids has been a challenge for synthetic chemists so far. These stemonamine alkaloids are isolated as racemates and there is no report concerning their asymmetric total synthesis. It is generally understood that any pair of enantiomers have physically and chemically indistinguishable properties. However, stereochemistry is a critical point in biological systems because most biological reactions, such as those mediated by enzymes and receptors, are stereospecific. We have successfully established the methods of asymmetric total synthesis of the stemonamine alkaloids, (–)-stemonamine/(–)-isostemonamine. We studied the potential application of these Stemona alkaloids as anti-proliferative agents. Experiments were conducted by using two representative human breast cancer cell lines, MCF-7 and MDA-MB-231, and our results indicated that i) (–)-isostemonamine displays strong cytotoxic effects on the highly aggressive estrogen receptor α (ERα)-negative MDA-MB-231 cell line, but not on the ERα-positive MCF-7 cells, with an IC50 value (9.3 ± 1.9 μM), which is comparable to that of etoposide (IC50 = 7.1 μM ± 1.4 μM), and ii) the thioamide derivative of (–)-isostemonamine does not suppress the growth of MDAMB-231 cells.