P-13 Microcolin誘導体の合成と生物活性(ポスター発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
During the course of our program aiming at developing natural products as biological probes to identify novel proteins for the exploration of molecular and cellular biology, we focused on microcolin A (1) and B (2). 1 and 2 are potent immunosuppressive and antiproliferative natural products, which were isolated from the marine cyanobacterium Lyngbya majuscula by Koehn et al. First in order to examine the structure-activity relationships, three microcolin derivatives (3-5) were designed and synthesized. The synthesized products were tested for the murine mixed lymphocyte reaction, the antiproliferative activity in murine lymphocytes stimulated by PMA plus ionomycin, and the antiproliferative effect on several cell lines. We found that microcolin A analog (3) inhibited the proliferation of all cell lines tested in this study in the low nanomolar range. 4-epi-microcolin A analog (4) and microcolin B analog (5) showed the antiproliferative activity against EL-4 and P-388 cells at 5-7μM, indicating that 4 and 5 were 100 times less potent than 3. These results suggest that the stereochemistry at C4 as well as the hydroxyl group at C10 would be important for the activity. Next in order to identify the target proteins of microclins, we designed and prepared the biotinylated microcolin A (28). Although 28 had the least biological activity of all the analogs tested in this study, it can still serve as a useful probe for elucidating the mechanism of action of microcolins. Now we are trying to elucidate the target molecules by affinity chromatographic techniques.
- 天然有機化合物討論会の論文
- 2005-09-15