Isolation, Synthesis, and Semisynthesis of Amaryllidaceae Constituents from Narcissus and Galanthus sp.: De Novo Total Synthesis of 2-epi-Narciclasine

Borra, Suresh; Lapinskaitė, Ringailė; Kempthorne, Christine J.; Liscombe, David K.; McNulty, James; Hudlický, Tomáš

doi:10.1021/acs.jnatprod.8b00218

Cited by 24 publications

(16 citation statements)

References 34 publications

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“…2-epi-narciclasine (Borra et al, 2018) Narcissus sp. (plant) 4 13 3 4 9 4,5 (+)-psiguadial B (Chapman et al, 2018) Psidium guajava (plant) 6 23 1 7 15 1,3…”

Section: Discussionunclassified

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Lautie

Russo

Ducrot³

2020

Front. Pharmacol.

166

120

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The screening and testing of extracts against a variety of pharmacological targets in order to benefit from the immense natural chemical diversity is a concern in many laboratories worldwide. And several successes have been recorded in finding new actives in natural products, some of which have become new drugs or new sources of inspiration for drugs. But in view of the vast amount of research on the subject, it is surprising that not more drug candidates were found. In our view, it is fundamental to reflect upon the approaches of such drug discovery programs and the technical processes that are used, along with their inherent difficulties and biases. Based on an extensive survey of recent publications, we discuss the origin and the variety of natural chemical diversity as well as the strategies to having the potential to embrace this diversity. It seemed to us that some of the difficulties of the area could be related with the technical approaches that are used, so the present review begins with synthetizing some of the more used discovery strategies, exemplifying some key points, in order to address some of their limitations. It appears that one of the challenges of natural product-based drug discovery programs should be an easier access to renewable sources of plant-derived products. Maximizing the use of the data together with the exploration of chemical diversity while working on reasonable supply of natural product-based entities could be a way to answer this challenge. We suggested alternative ways to access and explore part of this chemical diversity with in vitro cultures. We also reinforced how important it was organizing and making available this worldwide knowledge in an "inventory" of natural products and their sources. And finally, we focused on strategies based on synthetic biology and syntheses that allow reaching industrial scale supply. Approaches based on the opportunities lying in untapped natural plant chemical diversity are also considered.

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“…2-epi-narciclasine (Borra et al, 2018) Narcissus sp. (plant) 4 13 3 4 9 4,5 (+)-psiguadial B (Chapman et al, 2018) Psidium guajava (plant) 6 23 1 7 15 1,3…”

Section: Discussionunclassified

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Lautie

Russo

Ducrot³

2020

Front. Pharmacol.

166

120

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“…Next, the gene expression profiles of H9c2 cells after aconitine treatment were determined by NGS of mRNA on an Illumina HiSeq 4000 platform . There were 817 differentially expressed genes identified between the control and aconitine‐treated groups, including 503 upregulated and 314 downregulated genes (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Aconitine induces cardiomyocyte damage by mitigating BNIP3‐dependent mitophagy and the TNFα‐NLRP3 signalling axis

Zhang

Wang

et al. 2019

Cell Proliferation

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Objectives Aconitine, the natural product extracted from Aconitum species, is widely used for the treatment of various diseases, including rheumatism, arthritis, bruises, fractures and pains. However, many studies have reported cardiotoxicity and neurotoxicity caused by aconitine, but the detailed mechanism underlying aconitine's effect on these processes remains unclear. Materials and methods The effects of aconitine on the inflammation, apoptosis and viability of H9c2 rat cardiomyocytes were evaluated by flow cytometry, Western blot, RNA sequencing and bioinformatics analysis. Results Aconitine suppressed cardiomyocyte proliferation and induced inflammation and apoptosis in a dose‐ and time‐dependent manner. These inflammatory damages could be reversed by a TNFα inhibitor and BNIP3‐mediated mitophagy. Consistent with the in vitro results, overexpression of BNIP3 in heart tissue partially suppressed the cardiotoxicity of aconitine by inhibiting apoptosis and the NLRP3 inflammasome. Conclusions Our findings lay a foundation for the application of a TNFα inhibitor and BNIP3 to aconitine‐induced cardiac toxicity prevention and therapy, thereby demonstrating potential for further investigation.

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“…Lately, it has also been found in the crude extracts of Narcissus pseudonarcissus L. and Galanthus sp. [7].…”

Section: Plant Sources Of Narcipriminementioning

confidence: 99%

“…Narciprimine is 4,7-dihydroxy- [1,3]dioxolo-[4,5j]phenanthridin-6(5H)-one with a molecular weight of 271.0493 g/mol, in agreement with the molecular formula C14H9NO5 (Figure 1). It is commonly isolated in the form of white powder and crystallized from analytically pure acetic acid or acetone as fine yellowish-white needles that melt at 310-315 °C and show strong yellow-green fluorescence [7,10,15]. Although the structure of narciprimine is related to several Amaryllidaceae alkaloids, this compound displays no basic properties as its nitrogen is amidic in nature.…”

Section: Physical Chemical and Chromatographic Aspectsmentioning

confidence: 99%

“…Several alkaloids belonging to this class have recently received great attention owing to their efficacy against several incurable diseases, mostly as interesting anticancer drug candidates [1,5,6]. The phenanthridone alkaloid, narciprimine (Figure 1) is a rare narciclasine-related metabolite, which was isolated from the bulbs of some Cyrtanthus, Galanthus, Lycoris, Narcissus, and Zephyranthes species [1,[7][8][9][10][11][12]. This alkaloid was reported to exhibit anticholinesterase effects in addition to antiproliferative and apoptosis-enhancing activities against some cancer cell lines [6,11,13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A review on the chemical and biological properties of the Amaryllidaceae alkaloid, narciprimine (1968-2020)

Boshra

Fahim

desouky

2021

Journal of advanced Biomedical and Pharmaceutical Sciences

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Amaryllidaceae occupies a prominent position among the most important alkaloid-rich plant families in the globe. Plants of this family show an exceptional ability to produce a myriad of structurally diverse alkaloids with noteworthy pharmacological and therapeutic potential. Of these alkaloids, narciprimine is a rare weakly basic phenanthridone alkaloid that was identified from some species belonging to the genera Cyrtanthus, Galanthus, Lycoris, Narcissus, and Zephyranthes. This alkaloid has attracted a lot of scientific attention in recent years thanks to its biological properties, including cytotoxic, anticancer, and anticholinesterase activities. Hence, this review affords a comprehensive focus on the chemical, spectral, and biological attributes of narciprimine; providing a future perspective for possible research on this valued Amaryllidaceae alkaloid.

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Isolation, Synthesis, and Semisynthesis of Amaryllidaceae Constituents from Narcissus and Galanthus sp.: De Novo Total Synthesis of 2-epi-Narciclasine

Cited by 24 publications

References 34 publications

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

Aconitine induces cardiomyocyte damage by mitigating BNIP3‐dependent mitophagy and the TNFα‐NLRP3 signalling axis

A review on the chemical and biological properties of the Amaryllidaceae alkaloid, narciprimine (1968-2020)

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