Aporphine alkaloid contents increase with moderate nitrogen supply in Annona diversifolia Saff. (Annonaceae) seedlings during diurnal periods

Aporphine alkaloids are secondary metabolites that are obtained in low levels from species of the Annonaceae family. Nitrogen addition may increase the alkaloid content in plants. However, previous studies published did not consider that nitrogen could change the alkaloid content throughout the day. We conducted this short-term study to determine the effects of nitrogen applied throughout the diurnal period on the aporphine alkaloids via measurements conducted on the roots, stems and leaves of Annona diversifolia seedlings. The 60-day-old seedlings were cultured with the addition of three levels of nitrogen (0, 30 and 60 mM), and alkaloid extracts were analysed using high-performance liquid chromatography. The highest total alkaloid content was measured in the treatment with moderate nitrogen supply. Further, the levels of aporphine alkaloids changed significantly in the first few hours of the diurnal period. We conclude that aporphine alkaloid content increased with moderate nitrogen supply and exhibited diurnal variation.     

Chemical constituents of Talauma arcabucoana (Magnoliaceae): their brine shrimp lethality and antimicrobial activity

A new aporphine alkaloid, (-)-arcabucoine [(6aR)-N-formyl-1,2-methylenedioxy-9,10-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline] 1 was isolated from the leaves of Talauma arcabucoana (Magnoliaceae), along with the known compounds (-)-erythro-saccharinic acid lactone 2 and (-)-shikimic acid 3. Furthermore, the known aporphine alkaloids (-)-dicentrine 4, (-)-nordicentrine 5 and dicentrinone 6 were isolated from the stem bark. The alkaloids 4 and 5 were found to be the most active compounds in a brine shrimp lethality assay. In addition, alkaloids 1, 4 and 5 showed moderate growth inhibition against Staphylococcus aureus and Candida albicans.     

(+)‐N‐Formylnorglaucine Rotamers from Unonopsis stipitata Diels

(+)‐N‐formylnorglaucine ( 1 ), an aporphine alkaloid containing a formyl group linked to the heterocyclic nitrogen, was isolated from the leaves of Unonopsis stipitata, an Amazon medicinal plant. The chemical structure was characterized based on 1D‐ and 2D‐NMR spectroscopy and HR‐ESI‐MS. NMR spectra revealed that 1 is composed of two rotamers ( 1a and 1b ) in a ratio of approximately 2:1. In addition, the fragmentation behavior of 1 displayed an unusual fragmentation pattern compared to regular aporphine alkaloids. Thus, this compound is reported for the first time as a natural product in this study.     

Annonamine, a new aporphine alkaloid from the leaves of Annona muricata

Atypical Parkinsonism in the Caribbean Island Guadeloupe is thought to be associated with the consumption of plants of the Annonaceae family, especially Annona muricata (soursop). In this study, a new aporphine alkaloid named annonamine (1) was isolated from the leaves of A. muricata L. together with four known benzylisoquinoline alkaloids (2-5). The structures of the isolated compounds were elucidated by the spectroscopic method.     

A new aporphine alkaloid from Sabia yunnanensis

A new aporphine alkaloid, 1-hydroxy-2,3-dimethoxy-6-formyl-6a,7-dehydroaporphine, along with 15 known compounds have been isolated from the stems and leaves of Sabia yunnanensis. Their structures were established on the basis of spectral analysis.     

Isoquinoline alkaloids from Asimina triloba

A new aporphine glycoside, (-)-anolobine-9-O-β-D-glucopyranoside was isolated from the twigs of pawpaw (Asimina triloba) along with 7 known alkaloids including five aporphine alkaloids (anolobine, nornuciferine, norushinsunine, liriodenine, and lysicamine), a proaporhine alkaloid (stepharine), and a tetrahydrobenzylisoquinoline alkaloid (coclaurine). Among these compounds, nornuciferine, lysicamine, stepharine, and coclaurine are reported for the first time from this plant. The structure of the new compound was elucidated by spectroscopic methods, including 1?D, 2?D NMR, and HRESI-MS. The absolute configuration of compounds 1, 2, 7 and 8 was determined by CD experiment.     

Sesquiterpenes and alkaloids from Lindera chunii and their inhibitory activities against HIV-1 integrase

Three new eudesmane type sesquiterpenoid lindenanolides E (1), F (2) and G (3), and two new aporphine alkaloid lindechunines A (18) and B (20) were isolated from roots of Lindera chunii MERR., together with seven known sesquiterpenes including a new naturally-occurring lindenanolide H (4) and eight known aporphine alkaloids. The structures of these compounds were determined by spectroscopic means. Of the isolated compounds, hernandonine (14), laurolistine (16), 7-oxohernangerine (17) and lindechunine A (18) showed significant anti-human immunodeficiency virus type 1 (HIV-1) integrase activity with IC(50) values of 16.3, 7.7, 18.2 and 21.1 microM, respectively. The major alkaloids presented in the roots of L. chunii were quantitatively analyzed by an HPLC method.     

Bioactive isoquinoline alkaloids from Cissampelos pareira†

The phytochemical and biological investigation of Cissampelos pareira leads to the isolation of one new isoquinoline alkaloid (7) along with six known isoquinoline alkaloids, namely, magnoflorine (1), magnocurarine (2), cissamine (3), curine (4), hayatinine (5) and cycleanine (6). Magnoflorine (1) and magnocurarine (2) were isolated for the first time from C. pareira. A new, rapid, simple and sensitive UPLC method was developed for simultaneous quantification of five pure compounds (1–5). Seasonal variation study revealed higher content of these compounds during the rainy season. The chloroform (CPCF) and n-butanol (CPBF) fractions showed cytotoxic efficacy against KB cells. Among pure compounds, hayatinine (5) was found to be most active against KB and A549, while, cycleanine (6) against KB cells.     

Quantitative determination of isoquinoline alkaloids and chlorogenic acid in Berberis species using ultra high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometry

Berberis species are well known and used extensively as medicinal plants in traditional medicine. They have many medicinal values attributable to the presence of alkaloids having different pharmacological activities. In this study, a method was developed and validated as per international conference on harmonization guidelines using ultra high performance liquid chromatography with hybrid triple quadrupole‐linear ion trap mass spectrometry operated in the multiple reaction monitoring mode for nine bioactive compounds, including protoberberine alkaloids, aporphine alkaloids and chlorogenic acid. This method was applied in different plant parts of eight Berberis species to determine variations in content of nine bioactive compounds. The separation was achieved on an ACQUITY UPLC CSH? C₁₈ column using a gradient mobile phase at flow rate 0.3 mL/min. Calibration curves for all the nine analytes provided optimum linear detector response (with R² ≥0.9989) over the concentration range of 0.5–1000 ng/mL. The precision and accuracy were within RSDs ≤2.4 and ≤2.3%, respectively. The results indicated significant variation in the total contents of the nine compounds in Berberis species.     

Alkaloids ofLiriodendron tulipifera

The alkaloids of the tulip treeLiriodendron tulipifera L., family Magnoliaceae, are considered. More then 20 alkaloids have been isolated during different vegetation periods from various organs of the plant growing in Uzbekistan, and these have been assigned to the aporphine alkaloids and their dehydro, oxo, and 7-hydroxy derivatives; only two alkaloids proved to be derivatives of proaphorphine and of tetrahydroberberine. On the basis of the results of a comparative study of the NMR spectra of aporphines unsubstituted in ring D and some chemical transformations, the structure and configuration of the (R)-3-hydroxy-1,2-dimethoxyaporphine have been proposed for the new alkaloid lirinine. The absolute configurations, possible biogenetic interconnections, and mutual transitions of the alkaloids ofL. tylipifera that are derivatives of aporphine, oxoaporphine, and dehydroaporphine are discussed. A summery table is given which includes 41 alkaloids found in this plant.     

Alkaloids of the epigeal part ofAconitum karakolicum

The dynamics of the accumulation of alkaloids in the epigeal part ofAconitum karakolicum according to vegetation periods has been studied. It has been established that the highest content of alkaloids is found in the early period. On separating the combined alkaloids, the aporphine alkaloid isoboldine has been isolated from this plant for the first time and a new base has been obtained — napelline N-oxide, the structure of which has been shown on the basis of the results of a study of spectral characteristics and direct transition to napelline.     

Selective separation of structure-related alkaloids in Rhizoma coptidis with "click" binaphthyl stationary phase and their structural elucidation with liquid chromatography-mass spectrometry

It is a new task to separate structure-related compounds into a fraction according to their structural characteristics in a complex traditional Chinese medicine (TCM). This method makes separation of the components of the sample simple and structural elucidation easy. In this study, selective separation of alkaloids in Rhizoma coptidis was realized on a "click" binaphthyl column possessing a planar conjugate structure. Three kinds of alkaloids, aporphine, tetrahydroprotoberberine and protoberberine in Rhizoma coptidis showed better retention than other compounds by virtue of π-π interactions with the stationary phase. Moreover, the "click" binaphthyl column could distinguish the aporphine and tetrahydroprotoberberine alkaloids possessing two benzene rings from the protoberberine alkaloids possessing three benzene rings. After separating on the "click" binaphthyl column, the fractions containing the alkaloids were collected and then analyzed with liquid chromatography-mass spectrometry (LC-MS). Totally, 23 alkaloids were identified, and among these alkaloids, three tetrahydroprotoberberine, two aporphine and seven protoberberine alkaloids were first found in Rhizoma coptidis. These newly found alkaloids are minor compounds, and they are always neglected without eliminating the interference of compounds in large amounts by pre-separation on the "click" binaphthyl column. The typical fragmentation pathways of each class of alkaloids were summarized to illustrate their structures. In the MS(2) spectrum, the loss of a molecule of dimethylamine ((CH(3))(2)NH) was observed as the characteristic loss of aporphine alkaloids. All the tetrahydroprotoberberine alkaloids would undergo the Retro-Diels-Alder (RDA) fragmentation reaction in the MS(2) fragmentation. For protoberberine alkaloids, different characteristic fragmentations were observed with different skeleton structures.     

Two New Aporphine Alkaloids from Amoora cucullata and their Antibacterial Activity

Chemistry of Natural Compounds - Two new aporphine alkaloids, amocurines D and E (1 and 2), together with five known compounds (3–7), were isolated from the stems of Amoora cucullata. The...     

Toxicological evaluation in silico and in vivo of secondary metabolites of Cissampelos sympodialis in Mus musculus mice following inhalation

The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.     

Alkaloidal constituents of Tinospora crispa

Phytochemical investigations of the stems of Tinospora crispa led to the isolation of one new aporphine alkaloid, N-formylasimilobine 2-O-beta-D-glucopyranoside (1), along with six known alkaloids, N-formylasimilobine 2-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside (2) (tinoscorside A), N-formylanonaine (3), N-formyldehydroanonaine (4), N-formylnomuciferine (5), N-demethyl-N-formyldehydronornuciferine (6), magnoflorine (7), paprazine (8), N-trans-feruloyltyramine (9), and cytidine (10). The structure of new compound 1 was deduced on the basis of spectroscopic data.     

Antineoplastic Alkaloids From Chinese Medicinal Plants and Their Analogs

The Chinese medicinal plant-derived antineoplastic alkaloids and their analogs are reviewed with emphasis on those discovered from the authors' laboratory. The active compounds include camptothecin, colchicine, ellipticine, harringtonine, Vinca alkaloids, indirubin, (-)-sophocarpine, lycobetaine, monocrotaline, d-tetrandrine, indicine N-oxide, maytansine, aporphine type alkaloids, palmatine, murrapanine, emarginatine alkaloids, and the alkaloids from Securinega virosa. The compounds are discussed briefly with the recent advances concerning their antitumor activity, structure-activity relationships and mechanisms of action.     

Two new alkaloids from Narcissus serotinus L

The Amaryllidaceae family is well known for the presence of an exclusive group of alkaloids with a wide range of biological activities. Narcissus serotinus L. is a plant belonging to this family and its geographical distribution is mainly located along the Mediterranean coast. In the present work, specimens collected near Casablanca (Morocco) were used to study the alkaloid content of this species. Starting with 350 g of the whole plant we used standard extraction and purification procedures to obtain fractions and compounds for GC-MS and NMR analysis. As well as five known alkaloids, we isolated two new compounds: 1-O-(3′-acetoxybutanoyl)lycorine and narseronine. The latter has been previously published, but with an erroneous structure.     

Identification and metabolite profiling of alkaloids in aerial parts of Papaver rhoeas by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty‐five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine‐type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.     

Alkaloids ofLiriodendron tulipifera

The alkaloids of the tulip treeLiriodendron tulipifera L., family Magnoliaceae, are considered. More then 20 alkaloids have been isolated during different vegetation periods from various organs of the plant growing in Uzbekistan, and these have been assigned to the aporphine alkaloids and their dehydro, oxo, and 7-hydroxy derivatives; only two alkaloids proved to be derivatives of proaphorphine and of tetrahydroberberine. On the basis of the results of a comparative study of the NMR spectra of aporphines unsubstituted in ring D and some chemical transformations, the structure and configuration of the (R)-3-hydroxy-1,2-dimethoxyaporphine have been proposed for the new alkaloid lirinine. The absolute configurations, possible biogenetic interconnections, and mutual transitions of the alkaloids ofL. tylipifera that are derivatives of aporphine, oxoaporphine, and dehydroaporphine are discussed. A summery table is given which includes 41 alkaloids found in this plant.Institute of the Chemistry of Plant Substances of the Uzbek SSR, Academy of Sciences, Tashkent. Tashkent Agricultural Institute. Translated from Khimiya Prirodnykh Soedenii, No. 5, pp. 628–638, September–October, 1987.     

Preparative isolation of guaipyridine sesquiterpene alkaloid from Artemisia rupestris L. flowers using high-speed counter-current chromatography

Although the medicinal plant Artemisia rupestris L. has been widely researched for several decades, its alkaloids have never been isolated before. To our surprise, the alkaloids in the plant were not detected in the stems but detected in the flowers. Herein, a novel and strange guaipyridine sesquiterpene alkaloid with a carboxyl group named rupestine was purified successfully from the total alkaloids extracted from the flowers by high-speed counter-current chromatography (HSCCC). The two-phase solvent system used was composed of ethyl acetate-methanol-water (8:1:7, v/v/v). Fifty six milligrams of rupestine was obtained at over 97% purity and 95% recovery from 200 mg of the total alkaloids in one-step separation. Its structure was elucidated by spectroscopic methods including high resolution ESI-MS, (1)H NMR, (13)C NMR, Heteronuclear Multiple Bond Correlation (HMBC), Heteronuclear Single Quantum Coherence (HSQC), and Nuclear Overhauser Enhancement Spectroscopy (NOESY).