Norditerpenoid alkaloids from <i>Aconitum</i> and <i>Delphinium</i>: structural relevance in medicine, toxicology, and metabolism

Qasem, Ashraf M. A.; Zeng, Ziyu; Rowan, Michael G.; Blagbrough, Ian S.

doi:10.1039/d1np00029b

Cited by 24 publications

(40 citation statements)

References 83 publications

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“…Traditionally, Delphinium plants have been extensively utilized to treat arthritis and other inflammatory diseases, which implies that their major constituents, namely, diterpenoid alkaloids, possess certain anti-inflammatory activity. It has been reported in previous studies that a certain number of diterpenoid alkaloids, mainly aconitine-type and lycoctonine-type alkaloids, have exhibited in vitro anti-inflammatory activity ( Shen et al, 2020 ; Qasem et al, 2022 ). For example, two typical lycoctonine-type DAs, delbrunine and eldeline, from D. brunonianum Royle showed good anti-inflammatory activity in LPS-activated RAW 264.7 cells, which could significantly restrain the elevation of inflammatory factors, including NO, TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), COX-2 (cyclooxygenase 2), and iNOS (inducible nitric oxide synthase) through NF-κB signaling pathway ( Wang et al, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

Grandiflolines A–F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum

Yan

Jiang²,

Xiao-yan³

et al. 2022

Front. Chem.

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Delphinium grandiflorum L. (family Ranunculaceae), one of the most important and widely distributed Delphinium species, has received considerable interest due to its extremely high medicinal value. The discovery of novel metabolites from D. grandiflorum supported and broadened its application as an herbal medicine. In this study, the whole herb of D. grandiflorum was phytochemically investigated to obtain fourteen C19-lycaconitine-type diterpenoid alkaloids (1–14), including six undescribed alkaloids, grandiflolines A–F (1–6). The structural elucidation of them was accomplished by detailed spectroscopic analyses, mainly including HR-MS, 1D and 2D NMR (1H–1H COSY, NOESY, HMBC and HSQC), and IR spectra. New alkaloids 1–3 and 5 possess a characteristic △2,3 functional group in the A ring, while compounds 5 and 6 feature a rare OH-16 substituent. In addition, known compounds 7–12 were isolated from D. grandiflorum for the first time. Moreover, according to its medicinal use, new alkaloids 1–6 were estimated for their potential in vitro anti-inflammatory effects, and some of them exhibited inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages. Our work enriched the chemical diversity of D. grandiflorum and the genus Delphinium and presented beneficial information for further investigations.

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Section: Resultsmentioning

confidence: 99%

Grandiflolines A–F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum

Yan

Jiang²,

Xiao-yan³

et al. 2022

Front. Chem.

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“…The explanation reported by Wada and co-workers 10 for the stabilization of 1-OH NDA is that the introduced proton, which is the starting point of the fragmentation at position 8 ( Figure 5 B), is stabilized by an intramolecular hydrogen bond with 1-OH where ring A adopts a boat conformation. 15 On the other hand, 1-OMe NDA salts also form intramolecular H-bonds between the methoxy group and the protonated nitrogen, which flips ring A from a chair conformation into a boat 16 , 17 ( Figure 6 ) and results in a stabilization effect similar to 1-OH NDA. Therefore, the reported theory does not explain the observed higher fragmentation of 1-OMe NDA compared to 1-OH NDA.…”

Section: Resultsmentioning

confidence: 99%

Effect of Position 1 Substituent and Configuration on APCI–MS Fragmentation of Norditerpenoid Alkaloids Including 1-epi-Condelphine

2022

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Norditerpenoid alkaloids (NDA) are hexacyclic highly oxygenated compounds, and the analysis of their 3D configuration is important as it helps to interpret their bioactive conformations. High-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/MS–APCI) is a promising technique to investigate NDA stereochemistry. The effect of the alpha (α)-substituent at carbon 1 and its configuration on the stability of NDA in the mass spectrometer was studied. It was observed that 1-OH NDA are more stable compared to 1-OMe NDA due to the intramolecular H-bonding that exists in 1-OH NDA. In addition, 1-epi-condelphine 9 was found to be less stable in the mass spectrometer compared to condelphine 7 as the nitrogen is no longer hydrogen-bonded to the β-hydroxyl at position 1, which highlights the importance of the substituent configuration at carbon 1.

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“…After describing the skeleton of Compound 3, long range HMBC interaction (Figure 3) permitted the placement of the hydroxyl substituent at their respective positions, as the H-1 (δ4. 19) shows 2 J correlations with C-2 (δ 73.3) and C-10 (δ 44.0). Similarly, the HMBC coupling of terminal methylinic protons (δ 5.02 & 4.85) exhibited 1 J interaction with C-16 (δ 142) and 2 J interaction with C-12 (δ 78.3) and C-15(δ 26.9).…”

Section: Dft Calculation Of Compoundmentioning

confidence: 99%

“…Phytochemically, the genus Delphinium is reported to be a rich source of pharmacologically active diterpenoid alkaloids that pronounce potent antipyretic and analgesic activities. The nor-diterpenoid alkaloids have been found to show ten times more toxic effects as compared to any of the tested alkaloids [ 2 ]. A large number of natural products acting as cholinesterase inhibitors, especially diterpenoids and norditerpenoids alkaloids, have been investigated and isolated from different plant species as described extensively in recent studies [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense

Ahmad

Almehmadi

et al. 2022

Molecules

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This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol−1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.

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Norditerpenoid alkaloids from Aconitum and Delphinium: structural relevance in medicine, toxicology, and metabolism

Abstract: This highlight focuses on norditerpenoid alkaloids from Aconitum and Delphinium where their structural differences result in pharmacological diversity that ranges from poisons to drugs.

Cited by 24 publications

References 83 publications

Grandiflolines A–F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum

Grandiflolines A–F, new anti-inflammatory diterpenoid alkaloids isolated from Delphinium grandiflorum

Effect of Position 1 Substituent and Configuration on APCI–MS Fragmentation of Norditerpenoid Alkaloids Including 1-epi-Condelphine

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense

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