Cytotoxic Monoterpenoid Indole Alkaloids from <i>Tabernaemontana corymbosa</i> as Potent Autophagy Inhibitors by the Attenuation of Lysosomal Acidification

Zhang, Yu; Ding, Xiao; Yuan, Yu-Xi; Guo, Ling‐Li; Hao, Xiao‐Jiang

doi:10.1021/acs.jnatprod.9b00856

Cited by 24 publications

(5 citation statements)

References 29 publications

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“…Lysosome acidification blockade leads to lysosome dysfunction, which is related to the interruption of autophagy flux. Besides, the taberine D treatment did not observe a decrease in p62 protein expression, which confirmed that taberine D suppresses autophagy flux [ 244 ].…”

Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 82%

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

et al. 2022

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Regulated cell death (RCD) is a critical and active process that is controlled by specific signal transduction pathways and can be regulated by genetic signals or drug interventions. Meanwhile, RCD is closely related to the occurrence and therapy of multiple human cancers. Generally, RCD subroutines are the key signals of tumorigenesis, which are contributed to our better understanding of cancer pathogenesis and therapeutics. Indole alkaloids derived from natural sources are well defined for their outstanding biological and pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, and 3,3′-diindolylmethane, which are currently used in the clinic or under clinical assessment. Moreover, such compounds play a significant role in discovering novel anticancer agents. Thus, here we systemically summarized recent advances in indole alkaloids as anticancer agents by targeting different RCD subroutines, including the classical apoptosis and autophagic cell death signaling pathways as well as the crucial signaling pathways of other RCD subroutines, such as ferroptosis, mitotic catastrophe, necroptosis, and anoikis, in cancer. Moreover, we further discussed the cross talk between different RCD subroutines mediated by indole alkaloids and the combined strategies of multiple agents (e.g., 3,10-dibromofascaplysin combined with olaparib) to exhibit therapeutic potential against various cancers by regulating RCD subroutines. In short, the information provided in this review on the regulation of cell death by indole alkaloids against different targets is expected to be beneficial for the design of novel molecules with greater targeting and biological properties, thereby facilitating the development of new strategies for cancer therapy. Graphic abstract

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Section: Targeting Autophagic Signaling Pathways With Indole Alkaloid...mentioning

confidence: 82%

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

et al. 2022

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“…Optical rotations, HRESIMS, 1D and 2D NMR, ECD, and IR spectra were obtained as described previously [ 22 , 23 , 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, ibogaine is the most abundant ibogan-type MIA in the genus Tabernaemontana , and has been used as a psychopharmacological sacrament in the Bwiti religion (West Africa) for several centuries [ 21 ]. In recent years, various classes of MIAs have been isolated and identified from this genus and some of them possessed novel skeletons and intriguing biological activities [ 22 , 23 , 24 , 25 ]. Previously, we found that kopoffines A–C, which are MIA dimers, showed significant inhibition against cyclin-dependent kinase 5 and decreased the protein levels of phospho-tau (pTau217 and pTau396) without influencing A β production [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit β-Amyloid42 Production and Phospho-Tau (Thr217)

Han

Huang

et al. 2023

IJMS

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Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A–C (1–3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan–ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1–3 all reduce Aβ42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer’s disease [AD] associated with BACE1-, NCSTN-, GSK3β-, and CDK5-mediated pathways, suggesting these alkaloids’ potential against AD.

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“…Compounds 142 to 150 were isolated from the twigs and leaves of Tabernaemontana corymbose . Compounds 142 to 145 are vobasinyl-ibogaine-type alkaloids, with compound 142 additionally containing an unusual 1,3-oxazinane motif [ 48 ]. Compounds 151 and 152 were isolated from Mitragyna speciosa , while compounds 153 and 154 were isolated from Havil.…”

Section: Isolation Of Novel Indole Alkaloidsmentioning

confidence: 99%

“…However, only bisindoles were active, with the most potent inhibitor being taburnaemine D (EC 50 = 12.9 μM). The linkage pattern of the two indole units might be a crucial factor in determining the activities of the compound [ 48 ].…”

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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Cytotoxic Monoterpenoid Indole Alkaloids from Tabernaemontana corymbosa as Potent Autophagy Inhibitors by the Attenuation of Lysosomal Acidification

Cited by 24 publications

References 29 publications

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit β-Amyloid42 Production and Phospho-Tau (Thr217)

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

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