Vobatensines A–F, Cytotoxic Iboga-Vobasine Bisindoles from <i>Tabernaemontana corymbosa</i>

Sim, Dawn Su-Yin; Teoh, Wuen-Yew; Lim, Siew‐Huah; Thomas, Noel F.; Low, Yun‐Yee; Kam, Toh‐Seok

doi:10.1021/acs.jnatprod.5b01117

Cited by 29 publications

(32 citation statements)

References 28 publications

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“…[57] Vobatensines A-E (25a-e), isolated μM against most of the tested cancer cells. [58] Vobasinyl-iboga-type bisindole alkaloids taburnaemines A and C-I, isolated from the twigs and leaves of T. corymbosa, exhibited potential in vitro antiproliferative activity against A549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrugresistant KB cancer cell lines with IC 50 values of 2.6-9.8 μM (SRB assay). [59] Among them, the representative taburnaemine I (26; IC 50 :…”

Section: Bisindole Alkaloidsmentioning

confidence: 99%

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Zhang

2020

Archiv der Pharmazie

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The bisindole moiety, as a versatile pharmacophore, is one of the widespread heterocycles in naturally occurring and synthetic bioactive compounds. The bisindole alkaloids derived from natural sources possess structural and mechanistic diversity, and they were found to be generally more active than monoindole alkaloids against various cancer cell lines. Moreover, some bisindole alkaloids such as the tubulin inhibitors, vinorelbine and vinblastine, have already been approved for cancer therapy, suggesting that bisindole alkaloids are a significant source of anticancer agents and lead hits. Bisindole hybrids have the potential to overcome drug resistance, enhance efficiency, and reduce severe side effects. The bisindole–lactam hybrid midostaurin has already been approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia who are FLT3 mutation‐positive, highlighting the importance of bisindole hybrids in the development of novel anticancer agents. In this review, we present a brief account of the bisindole alkaloids derived from nature and of synthetic hybrids with potential anticancer activity developed in the recent 10 years.

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Section: Bisindole Alkaloidsmentioning

confidence: 99%

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Zhang

2020

Archiv der Pharmazie

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“…The crude methanol extract of V. africana was subjected to silica gel normal phase open column chromatography and elution with a gradient of ethyl acetate in hexane. Repeated column chromatography through Sephadex LH-20, preparative thin-layer chromatography (TLC) yielded a new bisindole alkaloid derivative named voacamine A (1) along with eight known compounds, voacangine (2), voacristine (3),coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8), and conoduramine (9) [16][17][18][19][20][21][22][23][24][25] (Figure 1). The structures of the compounds were established based on NMR ( Figures S3-S25) analyses as well as by comparison with published data.…”

Section: Isolation and Identification Of Alkaloidsmentioning

confidence: 99%

Compounds with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling

Babiaka¹,

Simoben²,

Abuga³

et al. 2020

Preprint

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A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds, voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8), and conoduramine (9), were isolated from the stem bark of Voacanga africana. The structures of the compounds were determined by comprehensive spectroscopic analyses (1D- and 2D-NMR). Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC50 values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the the O. ochengi thioredoxin reductase target and docking simulation attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilirial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.

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“…In addition to these compounds (which were obtained in minor amounts), the known bisindoles (Fig. 1A), viz., 16'-decarbomethoxyvoacamine (bisindole 1) [7][8][9] and its 19,…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative and Microtubule-stabilizing Activities of Two Iboga-vobasine Bisindoles Alkaloids from Tabernaemontana corymbosa in Colorectal Adenocarcinoma HT-29 Cells

et al. 2022

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Two iboga-vobasine bisindoles, 16'-decarbomethoxyvoacamine (1) and its 19,20-dihydro derivative, 16'-decarbomethoxydihydrovoacamine (2) from Tabernaemontana corymbosa exhibited potent cytotoxicity against the human colorectal adenocarcinoma HT-29 cells in our previous studies. Bisindoles 1 and 2 selectively inhibited the growth of HT-29 cells without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with bisindoles 1 and 2 suppressed the formation of HT-29 colonies via G0/G1 cell cycle arrest and induction of mitochondrial apoptosis. Owing to its higher antiproliferative activity, bisindole 2 was chosen for the subsequent studies. Bisindole 2 inhibited the formation of HT-29 spheroids (tumor-like cell aggregates) in 3D experiments in a dose-dependent manner, while an in vitro tubulin polymerization assay and molecular docking analysis showed that bisindole 2 is a microtubule-stabilizing agent which is predicted to bind at the β-tubulin subunit at the taxol-binding site. The binding resulted in the generation of ROS, which consequently activated the oxidative stress-related cell cycle arrest and apoptotic pathways, viz., JNK/p38, p21Cip1/Chk1, and p21Cip1/Rb/E2F, as shown by microarray profiling.

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Vobatensines A–F, Cytotoxic Iboga-Vobasine Bisindoles from Tabernaemontana corymbosa

Cited by 29 publications

References 28 publications

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids

Compounds with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling

Antiproliferative and Microtubule-stabilizing Activities of Two Iboga-vobasine Bisindoles Alkaloids from Tabernaemontana corymbosa in Colorectal Adenocarcinoma HT-29 Cells

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