Monoterpenoid Indole Alkaloids from Kopsia officinalis and the Immunosuppressive Activity of Rhazinilam

Abstract

Six new monoterpenoid indole alkaloids, kopsinidines C-E (1-3), 11,12-methylenedioxychanofruticosinic acid (4), 12-methoxychanofruticosinic acid (5), and N(4)-methylkopsininate (7), as well as chanofruticosinic acid (6, as a natural product) and 23 known alkaloids, were obtained from the twigs and leaves of Kopsia officinalis. Their structures were characterized by physical data analysis. All isolated compounds were evaluated for their immunosuppressive activity on human T cell proliferation. Rhazinilam (29) significantly inhibited human T cell proliferation activated by anti-CD3/anti-CD28 antibodies (IC = 1.0 μM) and alloantigen stimulation (IC = 1.1 μM) without obvious cytotoxicity for naïve human T cells and peripheral blood mononuclear cells (0-320 μM). Although it did not affect T cell activation, it induced T cell cycle arrest in the G/M phase and inhibited proinflammatory cytokine production in activated T cells.

Bioactivity-Guided Isolation and Identification of New and Immunosuppressive Monoterpenoid Indole Alkaloids from Rauvolfia yunnanensis Tsiang

“…All isolated compounds were evaluated for the inhibitory activity against human T cell proliferation according to reported protocols [17]. Compounds 1 and 6 showed immunosuppressive activity on human T cell proliferation, with IC 50 values of 5.9 µM and 5.0 µM, respectively.…”

“…The air-dried and powdered whole plants of R. yunnanensis (8.5 kg) were extracted as described before to yield CHCl 3 and n-BuOH extractions [17]. The CHCl 3 extraction (79.6 g) was subjected to silica gel CC eluted with a step gradient CHCl 3 -MeOH (50:1 to 0:1) system.…”

“…Yohimbine in combination with berberine has an immunoregulatory effect [16]. In our ongoing search for immunosuppressive compounds from medicinal plants [17], the total alkaloid extracts of whole R. yunnanensis plants exhibited promising immunosuppressive activity on T cell proliferation. Therefore, a comprehensive phytochemical investigation on the total alkaloids was carried out.…”

Thiourea‐Catalyzed Asymmetric Michael Addition of Carbazolones to 2‐Chloroacrylonitrile: Total Synthesis of 5,22‐Dioxokopsane, Kopsinidine C, and Demethoxycarbonylkopsin

“…Subjecting 24 to a similar reaction sequence as described above gave 26 and demethoxycarbonylkopsin sequentially, whose structures were unambiguously determined by X‐ray crystallographic analysis . Further reduction of the ketone with LiAlH 4 produced kopsinidine C and its epimer. Notably, our 1 H and 13 C NMR data of demethoxycarbonylkopsin were identical to those reported by the Qin group, but not in agreement with those taken from natural demethoxycarbonylkopsin, as mentioned by Qin and co‐workers.…”

“…Further reduction of the ketone with LiAlH 4 produced kopsinidine C and its epimer. Notably, our 1 H and 13 C NMR data of demethoxycarbonylkopsin were identical to those reported by the Qin group, but not in agreement with those taken from natural demethoxycarbonylkopsin, as mentioned by Qin and co‐workers. We found that this problem could be solved by adding a trace amount of TFA when collecting NMR spectroscopic data.…”