Lumutinines A−D, linearly fused macroline−macroline and macroline−sarpagine bisindoles from alstonia macrophylla

Four new linearly fused bisindole alkaloids, lumutinines A−D (1−4), were isolated from the stem-bark extract of Alstonia macrophylla. Lumutinines A (1) and B (2) represent the first examples of linear, ring A/F-fused macroline−macroline-type bisindoles, while lumutinines C (3) and D (4) were constituted from the union of macroline and sarpagine moieties. A reinvestigation of the stereochemical assignment of alstoumerine (8) by NMR and X-ray diffraction analyses indicated that the configuration at C-16 and C-19 required revision

Macroline–sarpagine and macroline–pleiocarpamine bisindole alkaloids from Alstonia angustifolia

Nine bisindole alkaloids, comprising four belonging to the macroline–sarpagine group, and five belonging to the macroline–pleiocarpamine group, were isolated from the stem-bark extracts of Alstonia angustifolia(Apocynacea). Their structures were established using NMR and MS analyses

Rhazinilam−leuconolam−leuconoxine alkaloids from leuconotis griffithii

Eight new indole alkaloids (1–8) belonging to the rhazinilam–leuconolam–leuconoxine group, in addition to 52 other alkaloids, were isolated from the stem-bark extract of Leuconotis griffithii, viz., nor-rhazinicine (1), 5,21-dihydrorhazinilam-N-oxide (2), 3,14-dehydroleuconolam (3), and leuconodines A–E (4–8). The structures of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 1, 5, and 7 showed only moderate to weak cytotoxicity toward KB cells (IC50 12–18 μg/mL), while 8 showed moderate activity in reversing MDR in vincristine-resistant KB cells

Macrodasines A—G, macroline indole alkaloids incorporating fused spirocyclic tetrahydrofuran—tetrahydrofuran and tetrahydrofuran—tetrahydropyran rings

The bark extract of the Malayan Alstonia angustifoliaWall provided the spirocyclic alkaloids macrodasines A—G. The structures of the new compounds were established by analysis of the spectroscopic data and in the case of macrodasines A and B confirmed by X-ray diffraction analysis. Macrodasines A, B, C, and G incorporate fused spirocyclic tetrahydrofuran—tetrahydrofuran rings, while macrodasines D, E, and F incorporate fused tetrahydrofuran—tetrahydropyran rings. Macrodasines B, C, and E were found to show moderate levels of activity in reversing multidrug-resistance in drug-resistant KB cells

Synergistic cytotoxic effects of combined δ-tocotrienol and jerantinine B on human brain and colon cancers

Ethnopharmacological relevance The genus Tabernaemontana has widespread distribution throughout tropical and subtropical parts of the world, i.e. Africa, Asia and America which has long been used for treatments of different disease conditions including tumours, wounds, syphilis, stomach ache and headache. Some Tabernaemontana species are used for treatment of piles, spleen and abdominal tumours in India. In particular, the leaf of Tabernaemontana corymbosa is used for treatment of tumours in Bangladesh. Parts of the plant or whole plants are used as decoctions, steam bath, powder and ointments. Aim of study The present study was undertaken to study the mechanism of apoptosis induction in human glioblastoma (U87MG) and colorectal adenocarcinoma (HT-29) cancer cells by a novel indole alkaloid, jerantinine B isolated from T. corymbosa, δ-tocotrienol and the combined low-dose treatments of δ-tocotrienol with IC20 dose of jerantinine B. Materials and methods Cell viability, isobologram and combinational index (CI) analyses were used to determine the pharmacological interaction between combined treatments based on the IC50 values obtained. Fluorescence and histochemical staining techniques as well as comet assay were used for evaluating the morphological changes and DNA damage pattern, respectively. The effects of treatments on microtubules, caspase activity and cell death were determined using immunofluorescence technique, caspase colorimetric and neutral red uptake assays, respectively. Results Jerantinine B, δ-tocotrienol and combined low-dose treatments induced a dose-dependent growth inhibition against U87MG and HT-29 cells selectively with less toxicity acted towards the normal MRC5 cells. Synergistic growth inhibition observed with CI values of 0.85 and 0.77 for U87MG and HT-29 cells, resulting in up to 2-fold and 3.8-fold dose reduction of δ-tocotrienol and jerantinine B, respectively. U87MG and HT-29 cells exhibited morphological features of apoptosis and double stranded DNA breaks. Individual and combined treatments induced caspase 8 and 3 activities and cell death independent of caspase activation on U87MG and HT-29 cells. An increased caspase 9 activity was also evident on U87MG and HT-29 treated with combined treatments and HT-29 cells treated with jerantinine B. Jerantinine B and combined low-dose treatments with δ-tocotrienol undoubtedly disrupted the microtubule networks. Conclusion The present study demonstrated the mechanism for cytotoxic potency of δ-tocotrienol and jerantinine B against U87MG and HT-29 cells. Furthermore, combined low-dose treatments induced concurrent synergistic inhibition of cancer cell growth with concomitant dose reduction thus minimizing toxicity to normal cells and improving potency of δ-tocotrienol and jerantinine B

Development of an alkaloid–pyrone annulation: synthesis of pleiomaltinine

Methodology for the synthesis of alkaloid-pyrones using a novel pyrone annulation of β–carbolines and indoles with 3-siloxy-4-pyrones is reported. The approach has enabled semisynthesis of the unprecedented alkaloid-pyrone pleiomaltinine from the plant-derived indole-alkaloid pleiocarpamine

Leucoridines A-D, cytotoxic strychnos-strychnos bisindole alkaloids from leuconotis

Four new bisindole alkaloids of the Strychnos-Strychnos type, leucoridines A-D (1-4), were isolated from the stembark extract of Leuconotis griffithii. Alkaloids 1-4 showed moderate cytotoxicity against drug-sensitive and vincristineresistant human KB cells

Aspidospermatan–aspidospermatan and eburnane-sarpagine bisindole alkaloids from Leuconotis

Leucofoline and leuconoline, representing the first members of the aspidospermatan–aspidospermatan and eburnane-sarpagine subclasses of the bisindole alkaloids, respectively, were isolated from the Malayan Leuconotis griffithii. The structures of these bisindole alkaloids were established using NMR and MS analysis, and in the case of leuconoline, confirmed by X-ray diffraction analysis. Both alkaloids showed weak cytotoxicity towards human KB cells

Angustilobine and andranginine type indole alkaloids and an uleine–secovallesamine bisindole alkaloid from Alstonia angustiloba

A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells

Transformations of the 2,7-Seco aspidosperma alkaloid leuconolam, structure revision of epi-Leuconolam, and partial syntheses of leuconoxine and leuconodines A and F

Several transformations of the seco Aspidosperma alkaloid leuconolam were carried out. The based-induced reaction resulted in cyclization to yield two epimers, the major product corresponding to the optical antipode of a (+)-meloscine derivative. The structures and relative configuration of the products were confirmed by X-ray diffraction analysis. Reaction of leuconolam and epileuconolam with various acids, molecular bromine, and hydrogen gave results that indicated that the structure of the alkaloid, previously assigned as epi-leuconolam,was incorrect. This was confirmed by an X-ray diffraction analysis, which revealed that epi-leuconolam is in fact 6,7-dehydroleuconoxine. Short partial syntheses of the diazaspiro indole alkaloid leuconoxine and the new leuconoxine-type alkaloids leuconodines A and F were carried out