Gelselegine-gelsedine type bisindoles as well as the units from Gelsemium elegans with promoting proliferation of oral mucosa fibroblast cells.

Two undescribed bisindole alkaloids, gelseginedine A (1) and its rearranged gelseginedine B (2), and seven unreported gelselegine-type oxindole alkaloids (3-9) were isolated from the stems and leaves of Gelsemium elegans, together with five known alkaloids (10-14). Compounds 1 and 2 represented the first examples of gelselegine-gelsedine type alkaloids which bridged two units by a double bond. Their structures with absolute configurations were elucidated by means of HRESIMS, NMR and calculational chemistry. The performed bioassay revealed that 14 could promote the proliferation of human oral mucosa fibroblast cells.

Discovery and biological evaluation of a new type of dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase from ethnomedicinal plant Dactylicapnos scandens.

The root of Dactylicapnos scandens (D.Don.) Hutch (Papaveraceae), one of the most famous ethno-medicinal plants from the Bai communities in P. R. China, is used to treat various inflammations and tumours. Bioassay-guided phytochemical research on D. scandens followed by semi-synthesis led to a series of undescribed tetrahydroisoquinoline alkaloids with dual inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). The previously undescribed dark-green alkaloid dactycapnine A exhibited the best dual inhibitor effects among the identified compounds. Structure-activity relationship analysis revealed the importance of the base skeleton with a hyperconjugation system. The performed semi-synthesis further yielded bioactive dimeric and trimeric compounds with hyperconjugated systems. Performed STD NMR experiments disclosed direct interactions between dactycapnine A and IDO1/TDO. Inhibition kinetics indicated dactycapnine A as a mixed-type dual inhibitor. These findings provided a possible explanation for the anticancer properties of the ethno-medicinal plant species D. scandens.

Diverse aspidosperma-type alkaloids from the leaves of Tabernaemontana bovina with anti-hepatoma activity.

Seventeen undescribed Aspidosperma-type alkaloids (ASPs), along with nine known ones were isolated from the leaves of Tabernaemontana bovina. Taberbovermines A and B were assigned to tabersonine-type with a contracted A- and E-ring, respectively. Taberbovermine C was attributed to tabersonine without D ring. These structures of the ASPs were established on the basis of comprehensive spectroscopic data, electronic circular dichroism calculations and X-ray diffraction. The summaries of structure-activity relationship of tabersonine class were discussed based on hepatoma cells screening.

Anti-inflammatory maistemonine-class alkaloids of Stemona japonica.

Three hitherto undescribed Stemona alkaloids, named stemajapines A-C (1-3), along with six known alkaloids (4-9), were isolated and identified from the roots of Stemona japonica (Blume) Miq. (Stemonaceae). Their structures were established by the analysis of the mass data, NMR spectra, and computational chemistry. Stemjapines A and B were degraded maistemonines without spiro-lactone ring and skeletal methyl from maistemonine. Concurrence of alkaloids 1 and 2 revealed an undescribed way to form diverse Stemona alkaloids. Bioassay results disclosed the anti-inflammatory natural constituents stemjapines A and C with IC50 values of 19.7 and 13.8 µM, respectively, compared to positive control dexamethasone with 11.7 µM. The findings may point out a new direction of Stemona alkaloids inaddition to its traditional antitussive and insecticide activities.

Dimeric alkaloids from the barks of Erythrina variegata as well as their occurrence.

Thirteen undescribed dimeric Erythrina alkaloids, named as erythrivarines A1-A13, were isolated from the barks of Erythrina variegata L. and. Their structures were determined on the basis of NMR, UV and mass spectral analyses. Dimeric Erythrina alkaloid with a C-8/8' linkage in erythrivarine A1 was not yet reported. Representative dimers from titled plant were used to prove their occurrence as natural products by LC - MS detection. Additionally, simultaneous investigation enabled us to propose the natural property of seemingly artificial Erythrina alkaloid with acetonyl group.

Enantiomeric Cephalotaxus alkaloids from seeds of Cephalotaxus oliveri.

Five undescribed alkaloids were isolated from the seeds of Cephalotaxus oliveri along with 27 known ones. The new structures were elucidated based on spectroscopic data including 1D and 2D NMR, MS and calculated ECD spectra. Among them, (+)-acetylcephalofortine C was an enantiomeric Cephalotaxine alkaloids. The performed bioassay revealed that those alkaloids were not cytotoxic against cancer cells and had no neuroprotective properties in the HEI-OC-1 cells model.

Dimeric Erythrina alkaloids as well as their key units from Erythrina variegata.

Ten dimeric and two monomeric Erythrina alkaloids, all of them are undescribed, were isolated from the bark of Erythrina variegata L. and named as erythrivarines O-Z. Their structures were determined on the basis of NMR and UV-spectroscopy and mass spectrometry. Dimeric Erythrina alkaloids with a C-10/11' linkage in erythrivarine O and a C-7/10' connectivity in erythrivarines P-U are not yet reported. The two identified monomeric alkaloids may be the precursors of the described dimeric derivatives. These co-occurring dimeric and monomeric alkaloids enabled us to propose a possible biosynthetic pathway leading to these dimers. Their effects of preventing hearing loss were additionally evaluated and erythrivarine T showed as a potential protector of the House Ear Institute-Organ of Corti 1 (HEI-OC-1) cells against neomycin.

Trimeric and dimeric Aspidosperma-type alkaloids from leaves of Tabernaemontana divaricata 'Dwaft'.

Continued interest in bioactive monoterpenoid indole alkaloids and the purpose to explore the artificial cultivation influence on the chemical composition in the same plant species, 8 undescribed Aspidosperma-type alkaloids including two unprecedented trimers, taberdivarines A-B (1-2), and six new dimers, taberdivarines CH (3-8), together with 9 known bisindoles were isolated from the leaves of Tabernaemontana divaricata 'Dwaft'. Notably, taberdivarines A and B were the first cases of Aspidosperma-Aspidosperma-Aspidosperma-type alkaloids with furan ring linkage patterns of the natural products. Their structures were elucidated by comprehensive spectroscopic analyse. Compounds 1-8 were screened for the cytotoxicity against three human cancer cell lines, SMMC-7721, HT-29 and A549. Among them, Compound 6 exhibited significant activity against three cell lines with IC50 values of 0.30, 0.75 and 3.41 µM, respectively (IC50 = 3.02, 0.14 and 2.23 µM for the positive control, vinorelbine). Compound 1, 3, 4, 6, 7 and 8 also expressed varying degrees of activity. The structure-activity relationships (SARs) of these alkaloids were discussed.

Colored Dimeric Alkaloids from the Barks of Erythrina variegata and Their Neuroprotective Effects.

Five dimeric Erythrina alkaloids, named erythrivarines J-N, were isolated from the barks of Erythrina variegata L. (Fabaceae). The erythrivarines J-L featured a 6/6/5/6/6/5/6/6/6 ring system and super conjugated double bond systems, causing intense color from blue to wine red, while erythrivarines M-N looked orange. The structures of the isolated compounds were elucidated by 1D and 2D NMR experiments combined with MS and confirmed by the X-ray crystal diffraction technique. The performed bioassay using HEI-OC-1 cells revealed neuroprotective properties of erythrivarine N against the hearing loss causing antibiotics, neomycin.

Vincan- and eburnan-type alkaloids from Tabernaemontana bovina and their hypoglycemic activity.

Thirty-one Vincan- and two Eburnan-type alkaloids were isolated from the aerial parts of Tabernaemontana bovina, whereas 20 of them are described the first time. Within the purified alkaloids, the firstly described taberbovcamine A features a 6/5/6/6/5 ring system. All the chemical structures were elucidated by employing extensive spectroscopic, computational electronic circular dichroism and X-ray diffraction methods. The two Eburnan-type alkaloids, 10,11-dimethoxy-16-O-methyllisoeburnamenine and 10,11-dimethoxy-isoeburnamenine were simultaneously identified by using the mentioned spectroscopic methods. Within the identified alkaloids, 10-hydroxy-14,15-didehydrovincanmine, 14,15-didehydrovincanmine, 14,15-didehydroapovincanmine, and criocerine increased the glucose consumption in a L6 myotube model.

Cage-Monoterpenoid Quinoline Alkaloids with Neurite Growth Promoting Effects from the Fruits of Melodinus yunnanensis.

Meloyunnanines A-C, three alkaloids with an unprecedented skeleton, were isolated from fruits of Melodinus yunnanensis. The structures featuring a caged-6/6/5/6/5/5 ring system were elucidated by the analysis of comprehensive spectroscopic and X-ray data. Biosynthetically, meloyunnanines A-C were assigned to monoterpenoid quinoline alkaloids (MQAs), derived from monoterpenoid indole alkaloids through oxidation and rearrangement. These compounds together with three known Melodinus MQAs were evaluated for their neurotrophic activity and scandine N4-oxide exhibited significant effect.

Artificial Erythrina Alkaloids from Three Erythrina Plants, E. variegata, E. crista-galli and E. arborescens.

Fourteen unprecedented artificial Erythrina alkaloids were isolated from the Erythrina variegata, E. crista-galli and E. arborescens (Fabaceae). The structures of these alkaloids were determined by spectroscopic analyses. Their possible formations were proposed. All isolated compounds showed no cytotoxicity and hypoglycemic activity at cell screening bioassay.

Tabernabovines A-C: Three Monoterpenoid Indole Alkaloids from the Leaves of Tabernaemontana bovina.

Three monoterpenoid indole alkaloids (MIAs), tabernabovines A-C (1-3), were isolated from Tabernaemontana bovina. They were elucidated by spectroscopic data and computational calculations. Unlike precursors of MIAs, strictosidine and alstrostine A, alkaloid 1 consists of tryptamine and secologanin in a 2:1 ratio. Alkaloid 2 is a cage compound, and 3 possesses a bridged ring. Tabernabovine A exhibited inhibitory activity against NO production with IC50 44.1 µM compared to l-NMMA with IC50 of 48.6 µM.

Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activity.

Continued interest in bioactive alkaloids led to the isolation of four undescribed alkaloids along with 74 known ones from the aerial parts of Tabernaemontana bufalina Lour. The structures of the yet undescribed alkaloids were elucidated based on NMR, IR, UV, MS and CD spectroscopic data and X-ray crystal diffraction and, according to the plant source, named as taberhaines A-D (1-4). The known compounds comprised of 66 monoterpenoid indole, three carboline and five isoquinoline alkaloids. Among them, the known apparicine inhibited significantly the activity of xanthine oxidase, which plays an important role for gout, with an IC50 value of 0.65 µM, compared to the standard drug allopurinol (IC50 = 0.60 µM).

Four Yellow Monoterpenoid Quinoline Alkaloids from the Stem of Tabernaemontana bovina.

Four unprecedented yellow alkaloids named as taberbovines A-D (1-4) were isolated from stems of Tabernaemontana bovina Lour. Their structures were elucidated by the comprehensive spectroscopic data, computational chemistry, and X-ray crystal diffraction. Alkaloids 1-4 possessed a unique 6/6/5/6/5 ring system and were assigned to monoterpenoid quinolines. Biosynthetically, the isolated alkaloids may be derived from Aspidosperma-type alkaloid by oxidation and rearrangements. Taberbovines A-D exhibited the good inhibitory activities of formation NO in LPS induced RAW264.7 macrophages.

A new erythrinan N-oxide alkaloid from Erythrina stricta.

This phytochemical study of stems and leaves of Erythrina stricta led to the isolation of twenty-three alkaloids, one of them previously unreported, 11ß-hydroxyerythratidine N-oxide. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analyses including HSQC, HMBC, 1H-1H COSY, NOESY, as well as HRESIMS data in addition to comparison with reports in the literature.

Alkaloids from flowers of Erythrina corallodendron.

Two new Erythrina alkaloids, 10-oxo-erythrinine (1) erythrinine N-oxide (2) together with 23 known ones were obtained from the flowers of Erythrina corallodendron. The structures were determined based on analysis of their spectroscopic data. All compounds were first isolated from plants of Erythrina corallodendron.

Three New Indole Alkaloids from Tabernaemontana divaricata.

Three new monoterpene indole alkaloids, 3α-hydroxymethyl-ibogamine (1), 3α-acetatemethoxyl-ibogamine (2), 16α-hydroxyl-ibogamine (3) together with six known alkaloids were isolated from the branches and leaves of Tabernaemontana divaricata (Apocynaceae). The structures of these alkaloids were determined by spectroscopic analyses. All isolated compounds showed no significant cytotoxicity against SGC-7901 gastric cancer, HeLa, and A-549 lung cancer cell lines (IC50 > 20 µM).

Bisindole alkaloids from Tabernaemontana corymbosa.

Continued study in bioactive monoterpenoid alkaloids led to the isolation of nine undescribed alkaloids, taberyunines A-I, together with 32 known ones from the aerial parts of Tabernaemontana corymbosa Roxb. ex Wall (Apocynaceae). Among the undescribed alkaloids, taberyunines A-G and H-I were assigned to Aspidosperma-Aspidosperma and Vobasinyl-Ibogan type bisindoles, respectively. Their structures were determined by NMR spectra, MS data and X-ray diffraction. Taberyunine B showed significant cytotoxicity against three cancer cell lines.

Bioactive norditerpenoids from Cephalotaxus fortunei var. alpina and C. lanceolata.

Twenty-eight naturally occurring Cephalotaxus tropone analogues, including 19 previously undescribed ones, were identified from Cephalotaxus fortunei Hook. var. alpina H. L. Li and C. lanceolata K. M. Feng. The presence of the C20 cephinoids A-E revealed that these tropones were assigned to the norditerpenoids and were perhaps derived from labdane-type diterpenoids. These norditerpenoids showed excellent cytotoxicity against human cancer cells (IC50, 20-0.1 µM) in vitro. The SAR (structure-activity relationship) analysis disclosed that the tropone moiety and the lactone ring were crucial structural features for the observed activities. Further SAR analyses led to a new candidate, cephinoid H, which demonstrated an inhibition of 49.0% by administration to zebrafish at a dose of 60.0 ng/mL, compared to cisplatin (DDP, 22.4%) at 15.0 µg/mL. These compounds might affect the NF-κB signaling pathway rather than binding to microtubules. Additionally, the isolated norditerpenoids showed almost equal anti-inflammatory activities compared to the positive control, MG132.