Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives

Ghavre, Mukund; Froese, Jordan; Pour, Milan; Hudlický, Tomáš

doi:10.1002/anie.201508227

Cited by 77 publications

(72 citation statements)

References 242 publications

(671 reference statements)

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“…For instance, several studies have demonstrated that lycorine displays remarkable efficacy in the suppression of tumorigenesis (14,(19)(20)(21)(22)(23). However, the underlying mechanism involved remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Although the targets or mechanisms of lycorine are still undefined, the dominant biological effects and low cytotoxicity of lycorine render it as a potential clinical drug or lead. For instance, it has received much attention as a promising anticancer agent for bladder cancer, cervical cancer, leukemia, prostate cancer, and multiple myeloma (14,(19)(20)(21)(22)(23). However, the defined molecular mechanisms underlying lycorine-regulated suppression of tumorigenesis remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Qiu

Pang

et al. 2017

Molecular Cancer Therapeutics

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Lycorine is a multifunctional bioactive compound, and it possesses potential anticancer activities. However, little is known about the underlying mechanism. In this research, we have found that lycorine significantly induces the apoptotic and autophagic capacities of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Treatment with specific autophagy inhibitor (3-methyladenine/Bafilomycin A1) or knockdown of LC-3B/Atg5 by siRNA drastically enhances the apoptotic cell death effect by facilitating the switch from autophagy to apoptosis. Molecular validation mechanistically demonstrates that lycorine-induced apoptosis and autophagy in HCC cells is associated with decreased protein levels of tongue cancer resistance-associated protein 1 (TCRP1), and we further find that inhibition of TCRP1 decreases phosphorylation level of Akt and represses Akt/mTOR signaling. Finally, lycorineinduced apoptosis and autophagy suppress the growth of xenograft hepatocellular tumors without remarkable toxicity. Our results elucidate a novel molecular mechanism whereby lycorine promotes apoptosis and autophagy through the TCRP1/Akt/mTOR pathway in HCC. Our results reveal that lycorine might be a potential therapeutic agent for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Qiu

Pang

et al. 2017

Molecular Cancer Therapeutics

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“…The commercial ( S )‐2‐(methoxymethyl)pyrrolidine [( S )‐ 273 e ] was proven to be the most effective substrate leading up to 81 % ee of (−)‐ 270 (>99 % ee after crystallization). This accomplishment was also employed in Alonso's creative synthesis of (+)‐pancratistatin (the furyl unit in 270 was replaced by the aromatic A‐ring common to the Amaryllidaceae alkaloids) . The best conditions to obtain (+)‐ 270 required for the enantioselective synthesis of Sato's intermediate 158 involved the utilization of ( R )‐2‐(methoxymethyl)pyrrolidine [( R )‐ 273 e ] and provided 270 in 39 % yield with 77 % ee or in 42 % with 74 % ee, depending on the solvent.…”

Section: Synthesis Of Ttxmentioning

confidence: 99%

Tetrodotoxin: History, Biology, and Synthesis

et al. 2019

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This review provides a comprehensive coverage of the history, biology and chemistry of tetrodotoxin (TTX). It traces the origin of this remarkable molecule all the way back to the ancient Chinese medicine records. The discovery of biological activity, isolation, and a brief overview of structure elucidation are summarized. Next, the biology of TTX is discussed, primarily in the context of its activity in the sodium channels, its anesthetic properties, and its potential use in cancer treatment or drug addiction. Biosynthesis of TTX is covered before the discussion of the total syntheses. All total, formal or partial syntheses are covered but those total syntheses that have been discussed in previous reviews are only briefly summarized. Finally, the synthesis of natural and unnatural derivatives is surveyed, and a conclusion and outlook are provided for this very extensive field of endeavor. To the best of our knowledge the literature coverage is complete up to December 2018.

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“…Natural products possess multiple bioactivities and serve as excellent drug leads for cancer treatment [5][6][7]. Lycorine, an active alkaloid extracted from a common herbal medicine (Lycoris radiate), was reported to possess anti-viral, anti-inflammatory and anti-cancer activities [8][9][10]. Notably, it has been found that lycorine can suppress the development of various malignant tumors, including multiple myeloma, hepatocellular carcinoma, and prostate cancer [11][12][13].…”

mentioning

confidence: 99%

Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway

Jiang¹,

Liu²

2018

Med Sci (Paris)

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Malignant melanoma, one of the most aggressive skin cancers, has a very high mortality rate. Currently, the number of drugs to treat melanoma is low. Although new immunotherapeutic approaches based on the use of antibodies against immune checkpoints have shown long term responses, it is urgent to develop novel anti-melanoma drugs with a high efficiency and a low toxicity in a large number of patients. Lycorine, a natural product, has been reported to exert antitumor effects on some cancers. However, the impact of lycorine on melanoma cells is still unknown. Using the CCK8 assay, we found that lycorine can suppress the proliferation of melanoma A375 cells in a dose-time-dependent manner. Moreover, a transwell assay showed that lycorine inhibited the migration and invasion of A375 cells significantly. Further, lycorine treatment could induce the apoptosis of the A375 cells. Biochemical analyses showed that the expression level of the anti-apoptosis Bcl-2 protein decreased, while the expression of the pro-apoptosis protein Bax and active caspase-3 increased after lycorine treatment. Finally, using western blot assay, we found that the antitumor effects of lycorine on A375 cells might be through the inactivation of the PI3K/Akt signaling pathway. Based on these observations, we suggest that lycorine may be an interesting candidate for further studies on its ability to represent a novel antitumor drug for human melanoma treatment in the future.

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Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives

Cited by 77 publications

References 242 publications

Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Lycorine Promotes Autophagy and Apoptosis via TCRP1/Akt/mTOR Axis Inactivation in Human Hepatocellular Carcinoma

Tetrodotoxin: History, Biology, and Synthesis

Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway

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