Tabernaesines A–I, Cytotoxic Aspidosperma–Aspidosperma-Type Bisindole Alkaloids from <i>Tabernaemontana pachysiphon</i>

Yi, Wen-Fang; Ding, Xiao; Chen, Yuan-Zhi; Adelakun, Tiwalade A.; Hao, Xiao‐Jiang

doi:10.1021/acs.jnatprod.9b00768

Cited by 23 publications

(4 citation statements)

References 19 publications

(37 reference statements)

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“…Globospiramine (1) demonstrated better IC 50 against A549 (IC 50 = 0.18 uM) and MDA-MB-231 (IC 50 = 0.387 uM) cells than all T. pachysiphon alkaloids (IC 50 > 8 uM) despite their high structural similarity. Some minor differences include the distinct presence of methoxy and the different spatial positions of hydroxylation in globospiramine (1), which may have contributed to its robust cytotoxicity [56].…”

Section: Discussionmentioning

confidence: 99%

Globospiramine from Voacanga globosa Exerts Robust Cytotoxic and Antiproliferative Activities on Cancer Cells by Inducing Caspase-Dependent Apoptosis in A549 Cells and Inhibiting MAPK14 (p38α): In Vitro and Computational Investigations

Manzano,

Abellanosa,

Aguilar

et al. 2024

Cells

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Bisindole alkaloids are a source of inspiration for the design and discovery of new-generation anticancer agents. In this study, we investigated the cytotoxic and antiproliferative activities of three spirobisindole alkaloids from the traditional anticancer Philippine medicinal plant Voacanga globosa, along with their mechanisms of action. Thus, the alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) showed in vitro cytotoxicity and antiproliferative activities against the tested cell lines (L929, KB3.1, A431, MCF-7, A549, PC-3, and SKOV-3) using MTT and CellTiter-Blue assays. Globospiramine (1) was also screened against a panel of breast cancer cell lines using the sulforhodamine B (SRB) assay and showed moderate cytotoxicity. It also promoted the activation of apoptotic effector caspases 3 and 7 using Caspase–Glo 3/7 and CellEvent-3/7 apoptosis assays. Increased expressions of cleaved caspase 3 and PARP in A549 cells treated with 1 were also observed. Apoptotic activity was also confirmed when globospiramine (1) failed to promote the rapid loss of membrane integrity according to the HeLa cell membrane permeability assay. Network pharmacology analysis, molecular docking, and molecular dynamics simulations identified MAPK14 (p38α), a pharmacological target leading to cancer cell apoptosis, as a putative target. Low toxicity risks and favorable drug-likeness were also predicted for 1. Overall, our study demonstrated the anticancer potentials and apoptotic mechanisms of globospiramine (1), validating the traditional medicinal use of Voacanga globosa.

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Section: Discussionmentioning

confidence: 99%

Globospiramine from Voacanga globosa Exerts Robust Cytotoxic and Antiproliferative Activities on Cancer Cells by Inducing Caspase-Dependent Apoptosis in A549 Cells and Inhibiting MAPK14 (p38α): In Vitro and Computational Investigations

Manzano,

Abellanosa,

Aguilar

et al. 2024

Cells

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“…They are all aspidosperma–aspidosperma-type alkaloids and possess a rare spiro heterocycle between their two constituent units. Compounds 190 and 191 contain an indole ring fused with an ( N , N -diethyl)methyl amino group [ 55 ].…”

Section: Isolation Of Novel Indole Alkaloidsmentioning

confidence: 99%

“…Furthermore, replacing a proton with a hydroxy group at C-2 causes a significantly suppressed activity ( 192 vs. 191 ). Stereochemistry ( 192 vs. 194 and 193 vs. 195 ) was also a foremost determinant of the activities of alkaloids; switching C-14′ from an S to R configuration significantly reduced their activities [ 55 ].…”

Section: Bioactivities Of Novel Indole Alkaloidsmentioning

confidence: 99%

Indole-Containing Natural Products 2019–2022: Isolations, Reappraisals, Syntheses, and Biological Activities

et al. 2022

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Indole alkaloids represent a large subset of natural products, with more than 4100 known compounds. The majority of these alkaloids are biologically active, with some exhibiting excellent antitumor, antibacterial, antiviral, antifungal, and antiplasmodial activities. Consequently, the natural products of this class have attracted considerable attention as potential leads for novel therapeutics and are routinely isolated, characterized, and profiled to gauge their biological potential. However, data on indole alkaloids, their various structures, and bioactivities are complex due to their diverse sources, such as plants, fungi, bacteria, sponges, tunicates, and bryozoans; thus, isolation methods produce an incredible trove of information. The situation is exacerbated when synthetic derivatives, as well as their structures, bioactivities, and synthetic schemes, are considered. Thus, to make such data comprehensive and inform researchers about the current field’s state, this review summarizes recent reports on novel indole alkaloids. It deals with the isolation and characterization of 250 novel indole alkaloids, a reappraisal of previously reported compounds, and total syntheses of indole alkaloids. In addition, several syntheses and semi-syntheses of indole-containing derivatives and their bioactivities are reported between January 2019 and July 2022.

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“…[ 1−7 ] In recent five years, our research group has systematically studied this genus and discovered a series of novel and biologically active MIAs, such as tabercorymines A and B, taburnaemines A—I, and tabernaesines A—I. [ 8‐10 ] To continue the discovery of bioactive alkaloids from this genus, a novel vincamine‐type MIAs ( 1 ) and a structurally related one ( 2 ) were isolated and identified from the leaves of T. pachysiphon (Figure 1). The isolation, structural elucidation, and the biological activity of the two isolates were herein discussed in this report.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Tabernaesine J, a Novel Vincamine‐Type Indole Alkaloid with 6/5/6/6/6/5/5 Heptacyclic‐Ring System Scaffold from Tabernaemontana pachysiphon

Adelakun

Bai

et al. 2021

Chin. J. Chem.

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Tabernaesine J (1), an unprecedented vincamine-type indole alkaloid with 6/5/6/6/6/5/5 heptacyclic-ring system, as well as one new biogenetically related vincamine-type indole alkaloid (2), were isolated from leaves of Tabernaemontana pachysiphon. Their structures were established by a combination of HRESIMS, NMR, single crystal X-ray diffraction, and ECD calculation. The unprecedented penta-lactone ring in tabernaesine J (1) was postulated to be derived from acetyl-CoA enolate anion. Alkaloid 2 combined with fluconazole has the potential to overcome fluconazole resistance in Candida albicans.

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Tabernaesines A–I, Cytotoxic Aspidosperma–Aspidosperma-Type Bisindole Alkaloids from Tabernaemontana pachysiphon

Cited by 23 publications

References 19 publications

Globospiramine from Voacanga globosa Exerts Robust Cytotoxic and Antiproliferative Activities on Cancer Cells by Inducing Caspase-Dependent Apoptosis in A549 Cells and Inhibiting MAPK14 (p38α): In Vitro and Computational Investigations

Globospiramine from Voacanga globosa Exerts Robust Cytotoxic and Antiproliferative Activities on Cancer Cells by Inducing Caspase-Dependent Apoptosis in A549 Cells and Inhibiting MAPK14 (p38α): In Vitro and Computational Investigations

Indole-Containing Natural Products 2019–2022: Isolations, Reappraisals, Syntheses, and Biological Activities

Tabernaesine J, a Novel Vincamine‐Type Indole Alkaloid with 6/5/6/6/6/5/5 Heptacyclic‐Ring System Scaffold from Tabernaemontana pachysiphon

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