Five new diterpenoid alkaloids from Aconitum sczukinii Turcz.

Ten diterpenoid alkaloids, including five new ones, sczukiniline A–E (1-5), were isolated from the root of Aconitum sczukinii. Their structures were elucidated based on the interpretation of spectroscopic data (HRESI-MS, IR, 1D- and 2D-NMR). Among the five new diterpenoid alkaloids, 1-3 are hetidine-type C₂₀-diterpenoid alkaloids, while compounds 4 and 5 are lycoctonine-type C₁₉-diterpenoid alkaloids. Noteworthily, sczukiniline A (1) features a novel ester group between C-12 and C-14, forming a D ring containing a lactone structure, resulting in a new skeleton of hetidine-type C₂₀-diterpenoid alkaloid.     

Alkaloids of Toddalia asiatica (Rutaceae)

Phytochemical investigation of the alkaloidal extract of the roots of Toddalia asiatica led to the isolation of a new seco-benzophenanthridine alkaloid (1) and twelve known alkaloids (2–13). The new structure was elucidated by means of spectroscopic analysis, and the known alkaloids were identified by comparison with the literature. Among these alkaloids, 1 and 5–7 were reported from the genus Toddalia for the first time. The distribution of the isolated alkaloids at genus/family level was presented via network analysis and their chemotaxonomic significance was also discussed.     

Alstiphyllanines E–H,picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter

Three new picraline-type alkaloids, alstiphyllanines E–G (1–3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5–20). Structures and stereochemistry of 1–4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na⁺-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A series of a hydroxy substituted derivatives 21–28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity. 10-Methoxy-N(1)-methylburnamine-17-O-veratrate (6) exhibited potent inhibitory activity, suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity. Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.     

Pyrrole alkaloids from the fruits of Morus alba

Phytochemical investigation of the fruits of Morus alba afforded seventeen pyrrole alkaloids including five new compounds. The structures of five new pyrrole alkaloids, named morroles B–F (4, 5, 7, 16 and 17), were determined on the basis of spectroscopic interpretations. 4-[Formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]butanoate (2) was synthesized by chemical reaction but first isolated from nature. Among isolated compounds, compounds 6 and 14 significantly inhibited pancreatic lipase activity.     

Acridone alkaloids from Vepris verdoorniana (Excell & Mendonça) Mziray (Rutaceae)

Two new acridone alkaloids, verdoocridone A (1) and B (4), together with fifteen known compounds were isolated from methanol extracts of the roots and leaves of Vepris verdoorniana. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI- and ESI–MS). The ¹³C NMR values of 1,2,3,5-tetramethoxy-N-methylacridone (2) and 5-methoxyaborinine (3) are also reported. The crude extracts and compounds (1-6) were tested for their antimicrobial activity. The test delivered moderate activities for crude extracts and compounds 1, 5 and 6 against the bacterium Staphylococcus aureus and the fungi Mucor meihei and Candida albicans with MIC values between 115 and 180 μg/mL for extracts and between 21.3 and 29.4 μM for compounds, compared to gentamycin with 0.2 μM and nystatin with 5.2 μM against both fungi. The determination of the radical scanvenging activity using 1,1-dephenyl-2-picrylhydrazyl (DPPH) assay gave moderate antioxidant values for all tested compounds, with IC₅₀ between 0.29 and 0.41 μM, compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) displaying 0.03 μM.     

Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors

Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1–5 were established on the basis of HR-EIMS, ¹H and ¹³C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1–5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.     

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC₅₀ value of 15.41?μM.     

Erythrinoid and indol alkaloids isolated from the seeds of Erythrina rubrinervia Kunth: Chemotaxonomic significance

In the present work, we report the isolation of five alkaloids from the seeds of Erythrina rubrinervia. Four of the isolated alkaloids are erythrinoid type alkaloids which were identified as erysodine (1), erysovine (2), erythraline (3) and erysotrine (4), plus an indolic alkaloid which was identified as hypaphorine (5). The analysis of spectroscopic data for the alkaloid l-hypaphorine shows that the published structure (5a) must be revised, and the correct structure is that depicted as the structure 5c. The chemical structures were elucidated by full spectroscopic analysis. The chemotaxonomic significance of those findings in the genus Erythrina is also discussed.     

Chemical constituents of Gardneria ovata wall

A phytochemical investigation on the aerial parts of Gardneria ovata Wall resulted in the isolation and identification of 14 compounds, including three gardneria glycoalkaloids (1–2 and 6), seven gardneria alkaloids (3–5 and 7–10), and four oxindole alkaloids (11–14). The structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS together with 1D and 2D NMR experiments. Compounds 1–2 and 11–14 are the first time reported from of G. ovate, while the compounds 3–4, 6, and 8 are also the characteristic secondary metabolites of the title plant. The chemotaxonomic significance and distribution of these monoterpenoid indole alkaloids in Gardneria genus are discussed.     

Three new C19-diterpenoid alkaloids from Delphinium tianshanicum W. T. Wang

Three new C₁₉-diterpenoid alkaloids, tianshanisine (1), tianshanine (2) and tianshanidine (3), together with six known C₁₉-diterpenoid alkaloids (4–9) were isolated from the whole herb of Delphinium tianshanicum W. T. Wang. Their structures were established on the basis of spectroscopic analyses, including HR-ESI-MS and 1D and 2D NMR.     

Three new hetisine-type diterpenoid alkaloids from Aconitum coreanum

Three new hetisine-type diterpenoid alkaloids, Guan-fu base V (GFV, 1), Guan-fu base W (GFW, 2) and Guan-fu base X (GFX, 3) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics. Their structures were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), ¹D and ²D NMR (¹H–¹H COSY, ROESY, HSQC and HMBC). GFX is the third N-oxygenated hetisine-type diterpenoid alkaloid isolated from A. coreanum.     

Phytochemical and chemotaxonomic study on Dictamnus angustifolius G. Don ex Sweet (Rutaceae)

A phytochemical investigation of Dictamnus angustifolius led to the isolation of 14 compounds, including six furoquinoline alkaloids (1–6), two sesquiterpenoids (7, 8) and six flavonoids (9–14). The structures of these compounds were identified by spectroscopic methods and a comparison of their data with those reported in the literature. This is the first report of three furoquinoline alkaloids 1–3 and six flavonoids 9–14 from the genus Dictamnus and the first isolation of compounds 4–8 from D. angustifolius. The chemotaxonomic significance of furoquinoline alkaloids and sesquiterpenoids has also been summarized.     

Isolation,leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis

Leishmaniasis is one of the most important neglected tropical diseases (NTDs) that are especially common among low-income populations in developing regions of Africa, Asia, and the Americas. Many natural products, particularly alkaloids, have been reported to have inhibitory activity against arginase, the key enzyme in the pathology caused by Leishmania sp. In this way, piperidine alkaloids (–)-cassine (1), (–)-spectaline (2), (–)-3-O-acetylcassine (3), and (–)-3-O-acetylspectaline (4) were isolated from Senna spectabilis flowers. These compounds (1/2 and 3/4) initially present as homologous mixtures were separated by high performance liquid chromatography and evaluated against the promastigote phase of Leishmania amazonensis. In addition, molecular docking simulations were implemented in order to probe the binding modes of the ligands 1–4 to the amino acids in the active site of L. amazonensis arginase. Alkaloid 2 (IC₅₀ 15.81?μg?mL^?1) was the most effective against L. amazonensis. Compounds 2 and 4, with larger side chain, were more effective against the parasite than compounds 1 and 3. The cell viability test on Vero cells revealed that compound 2 (CC₅₀ 66.67?μg?mL^?1) was the most toxic. The acetyl group in the 3-O position of the parent structures reduced the leishmanicidal activity and the toxicity of the alkaloids. Further, molecular docking suggested that Asn143 is essential for arginase to interact with (–)-spectaline-derived compounds, which agreed with the IC₅₀ measurements. Our findings revealed that S. spectabilis is an important source of piperidine alkaloids with leishmanicidal activity. Moreover, the natural compound 3 has been isolated for the first time. Experimental investigation combined with theoretical study advances knowledge about the enzyme binding site mode of interaction and contributes to the design of new bioactive drugs against Leishmania infection.     

Two new spirooxindole alkaloids from rhizosphere strain Streptomyces sp. xzqh-9

Two new spirooxindole alkaloids spindomycins A (1) and B (2) were isolated from rhizosphere strain Streptomyces sp. xzqh-9. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and MS data. The absolute configurations of 1 and 2 were determined by experimental and theoretical calculation of electronic circular dichroism (ECD). Antitumor, lactate dehydrogenase, and tyrosine kinase inhibitory activities of two compounds were evaluated, while only spindomycin B (2) exhibited weak inhibitory activity against tyrosine kinase Bcr-Abl.     

Two tetrahydroisoquinoline alkaloids from the fruit of Averrhoa carambola

The fruit of Averrhoa carambola, commonly known as star fruit or carambola, is popular in Southeast Asia and China. Two new tetrahydroisoquinoline alkaloids, (1R*,3S*)-1-(5-hydroxymethylfuran-2-yl)-3-carboxy-6-hydroxy-8-methoxyl-1,2,3,4-tetrahydroisoquinoline (1) and (1S*,3S*)-1-methyl-3-carboxy-6-hydroxy-8-methyoxyl-1,2,3,4-tetrahydroisoquinoline (2), were isolated from the fruit, along with vanillic acid (3), ferulic acid (4), 8,9,10-trihydroxythymol (5), and arjunolic acid (6). Their structures were elucidated by spectroscopic method. Compounds 1, 2, and 5 showed weak ferric reducing antioxidant potency (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity.     

New immunomodulatory steroidal alkaloids from Sarcococa saligna

Two new steroidal alkaloids, (20 S)-(bennzamido)-3β-(N,N-dimethyamino)-pregnane (1), and (20 S)-(bennzamido)-pregnane-3-one- (2), and two known steroidal alkaloids, pachysanaximine A (3) and 3β, 20α-diacetamido-5α-pregnane (4) were isolated from the whole plant of Sarcococca saligna. The structures of these compounds were identified with the help of spectroscopic techniques while spectra for known compounds were compared with spectra reported in literature. The immunomodulatory potential of the new compounds were found to be significant and dose dependent. Compound 1 showed inhibition of T cells proliferation at 10 μg/mL (95%), and inhibition of IL-2 production with an IC50 = 1.6 μg/mL.     

Isoquinoline alkaloids isolated from three Guatteria species

The chemical investigation of the aerial parts of Guatteria ferruginea collected in the National Park of Serra dos Órgãos, Teresópolis, Brazil and of Guatteria latifolia and Guatteria sellowiana collected in the National Park of Itatiaia, Itatiaia, Brazil resulted in the isolation and identification of six isoquinoline alkaloids, two aporphine alkaloids 3-hydroxy-nornuciferine (1), nornuciferine (2) and four oxoaporphine alkaloids lysicamine (3), isomoschatoline (4), liriodenine (5) and O-methylmoschatoline (6). The isoquinoline alkaloids were found in the species G. ferruginea, G. latifolia and G. sellowiana for the first time and they support the taxonomic position within the genus Guatteria. Isoquinoline alkaloids (5–6) can be considered chemotaxonomic markers of the subfamily Annonoideae.     

New purine alkaloids from the Red Sea marine tunicate Symplegma rubra

Investigation of the Red Sea marine tunicate Symplegma rubra Monniot, 1972 gave three new purine alkaloids namely 6-methoxy-7,9-dimethyl-8-oxoguanine (1), 6-methoxy-9-methyl-8-oxoguanine (2), and 2-methoxy-7-methyl-8-oxoadenine (4) together with seven known compounds: 6-methoxy-7-methyl-8-oxoguanine (3), 9-methyl-8-oxoadenine (5), 7-methyl-8-oxoadenine (6), 8-oxoadenine (7), 3-methylxanthine (8), inosine (9), and homarine (pyridinium-2-carboxylic acid-1-methyl) (10). Compound 6 was reported here for the first time from a natural source. The structure determination of the compounds was accomplished by extensive interpretation of their spectroscopic data including 1D (¹H and ¹³C) and 2D (¹H–¹H COSY, HSQC, and HMBC) NMR and high-resolution mass spectral data. The isolated compounds were evaluated for their protein kinase inhibitory activity against different kinases (CDK5, CK1, DyrK1A, and GSK3) at 10 μg/mL. The compounds showed moderate activity against these kinases.     

Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues

Twenty-five amide alkaloids (1–25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39–48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC₅₀ = 4.94 μM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC₅₀ >40 μM) against MDA-MB-231 and SK-BR-3. Structure–activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype.     

Geranylated carbazole alkaloids with potential neuroprotective activities from the stems and leaves of Clausena lansium

Clausena lansium (Lour.) Skeels is an evergreen small tree or shrub with great economic value, which belongs to the genus Clausena of the Rutaceae family. C. lansium is indigenous to Southern China, while currently widely cultivated in subtropical and tropical regions not only for the nutritional value and pharmacological uses of its fruits but also as a medicinal and ornamental plant. In this study, a systematic phytochemical study on the stems and leaves of C. lansium caused the separation and identification of two new geranylated carbazole alkaloids, clauselansiumines A (1) and B (2), as well as 10 known geranylated carbazole alkaloids (3–12). The chemical structures of these isolated geranylated carbazole alkaloids (1–12) were unambiguously determined based on comprehensive spectral data analyses. All these isolated geranylated carbazole alkaloids were tested for their neuroprotective effects against 6-hydroxydopamine induced cell death in human neuroblastoma SH-SY5Y cells in vitro. Compounds 1–12 displayed remarkable neuroprotective effects holding the EC₅₀ values ranging from 0.48 ± 0.04 to 12.36 ± 0.16 μM. These research results disclosed that the separation and purification of these geranylated carbazole alkaloids possessing remarkable neuroprotective effects separated from C. lansium could be extremely important to the discovery of new agents for the treatment and prevention for Parkinson's disease.