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Open AccessArticle

Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

by Emmy Tuenter, Karen Segers, Kyo Bin Kang, Johan Viaene, Sang Hyun Sung, Paul Cos, Louis Maes, Yvan Vander Heyden and Luc Pieters

Molecules 2017, 22(2), 224; https://doi.org/10.3390/molecules22020224 - 02 Feb 2017

Cited by 21 | Viewed by 5389

Abstract

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more [...] Read more.

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship) study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation) of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship) models were developed, using PLS (partial least squares regression) and MLR (multiple linear regression). On the one hand, these models allow for the indication of the most important descriptors (molecular properties) responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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3789 KiB

Open AccessArticle

Extraction and Quantification of Bioactive Tyrian Purple Precursors: A Comparative and Validation Study from the Hypobranchial Gland of a Muricid Dicathais orbita

by Roselyn Valles-Regino, Peter Mouatt, David Rudd, Lachlan H. Yee and Kirsten Benkendorff

Molecules 2016, 21(12), 1672; https://doi.org/10.3390/molecules21121672 - 05 Dec 2016

Cited by 12 | Viewed by 5774

Abstract

Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass [...] Read more.

Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass spectrometry (HPLC-MS) with diode array detector (DAD). Quantification of the dominant secondary metabolites from D. orbita is described, followed by a comparison of solvent extraction procedures and stability studies. The intra- and inter-day relative standard deviation (RSD) for tyrindoxyl sulphate was 0.46% and 0.17%, respectively. The quantification was linear for standards murexine, 6-bromoisatin, and tyrindoxyl sulphate. The limits of detection were 0.03, 0.004, and 0.07 mg/mL, respectively, and the limits of quantification were 0.09, 0.01, and 0.22 mg/mL, respectively. The results showed that alcoholic solvents were better for extracting choline ester and indoxyl sulphate ultimate precursors, while chloroform was more suitable for the extraction of the intermediate precursors. Multivariate analysis revealed significant differences in extract composition according to the solvent used. Stability testing showed an increase of the oxidative compounds 6-bromoisatin and putative tyrindoxyl S-oxide sulphate in the ethanol extracts while more degradation products were seen in the chloroform extracts after months of cold storage. The validated method was found to be simple, reproducible, precise, and suitable for quantification of the secondary metabolites of muricid molluscs for dye precursor and nutraceutical quality control, as well as applications in marine chemical ecology. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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558 KiB

Open AccessArticle

Bioactivities of a New Pyrrolidine Alkaloid from the Root Barks of Orixa japonica

by Xin Chao Liu, Daowan Lai, Qi Zhi Liu, Ligang Zhou, Qiyong Liu and Zhi Long Liu

Molecules 2016, 21(12), 1665; https://doi.org/10.3390/molecules21121665 - 02 Dec 2016

Cited by 33 | Viewed by 5599

Abstract

A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against [...] Read more.

A new pyrrolidine alkaloid named (Z)-3-(4-hydroxybenzylidene)-4-(4-hydroxyphenyl)-1-methylpyrrolidin-2-one was isolated from the ethanol extract of the root barks of Orixa japonica. The structure of the new alkaloid was elucidated on the basis of NMR and MS analysis. The compound exhibited larvicidal activity against the fourth instar larvae of Aedes aegypti (LC₅₀ = 232.09 μg/mL), Anopheles sinensis (LC₅₀ = 49.91 μg/mL), and Culex pipiens pallens (LC₅₀ = 161.10 μg/mL). The new alkaloid also possessed nematicidal activity against Bursaphelenchus xylophilus (LC₅₀ = 391.50 μg/mL) and Meloidogynein congnita (LC₅₀ = 134.51 μg/mL). The results indicate that the crude ethanol extract of O. japonica root barks and its isolated pyrrolidine alkaloid have potential for development into natural larvicides and nematicides. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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1061 KiB

Open AccessArticle

Penicitroamide, an Antimicrobial Metabolite with High Carbonylization from the Endophytic Fungus Penicillium sp. (NO. 24)

by Zi-Wei Feng, Meng-Meng Lv, Xue-Shuang Li, Liang Zhang, Cheng-Xiong Liu, Zhi-Yong Guo, Zhang-Shuang Deng, Kun Zou and Peter Proksch

Molecules 2016, 21(11), 1438; https://doi.org/10.3390/molecules21111438 - 28 Oct 2016

Cited by 10 | Viewed by 4535

Abstract

Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves [...] Read more.

Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves of Tapiscia sinensis Oliv. The structure of penicitroamide (1) features a bicyclo[3.2.1]octane core unit with a high degree of carbonylization (four carbonyl groups and one enol group). The chemical structure of penicitroamide (1) was elucidated by analysis of 1D-, 2D-NMR and MS data. In bioassays, penicitroamide (1) displayed antibacterial potency against two plant pathogens, Erwinia carotovora subsp. Carotovora (Jones) Bersey, et al. and Sclerotium rolfsii Sacc. with MIC₅₀ at 45 and 50 μg/mL. Compound 1 also showed 60% lethality against brine shrimp at 10 μg/mL. Penicitroamide (1) exhibited no significant activity against A549, Caski, HepG2 and MCF-7 cells with IC₅₀ > 50 μg/mL. Finally, the possible biosynthetic pathway of penicitroamide (1) was discussed. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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798 KiB

Open AccessArticle

Alkaloids with Activity against the Zika Virus Vector Aedes aegypti (L.)—Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine sarniensis

by Marco Masi, Antonio Cala, Nurhayat Tabanca, Alessio Cimmino, Ivan R. Green, Jeffrey R. Bloomquist, Willem A. L. Van Otterlo, Francisco A. Macias and Antonio Evidente

Molecules 2016, 21(11), 1432; https://doi.org/10.3390/molecules21111432 - 27 Oct 2016

Cited by 33 | Viewed by 6758

Abstract

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) [...] Read more.

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo[d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time. Compounds 1–6 were evaluated against the Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal activity with an LD₅₀ = 2.29 ± 0.049 μg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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2572 KiB

Open AccessArticle

C19-Norditerpenoid Alkaloids from Aconitum szechenyianum and Their Effects on LPS-Activated NO Production

by Fei Wang, Zhenggang Yue, Pei Xie, Li Zhang, Zhen Li, Bei Song, Zhishu Tang and Xiaomei Song

Molecules 2016, 21(9), 1175; https://doi.org/10.3390/molecules21091175 - 03 Sep 2016

Cited by 20 | Viewed by 5751

Abstract

Three new C₁₉-norditerpenoid alkaloids (1–3), along with two known C₁₉-norditerpenoid alkaloids (4–5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as [...] Read more.

Three new C₁₉-norditerpenoid alkaloids (1–3), along with two known C₁₉-norditerpenoid alkaloids (4–5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1–5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC₅₀ value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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6888 KiB

Open AccessArticle

Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2

by Qiaolin Dong, Ju Luo, Wen Qiu, Li Cai, Syed Ishtiaq Anjum, Bin Li, Mingsheng Hou, Guanlin Xie and Guochang Sun

Molecules 2016, 21(8), 978; https://doi.org/10.3390/molecules21080978 - 27 Jul 2016

Cited by 16 | Viewed by 6194

Abstract

Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial [...] Read more.

Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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1383 KiB

Open AccessArticle

Indole Alkaloids from the Leaves of Nauclea officinalis

by Long Fan, Cheng-Hui Liao, Qiang-Rong Kang, Kai Zheng, Ying-Chun Jiang and Zhen-Dan He

Molecules 2016, 21(8), 968; https://doi.org/10.3390/molecules21080968 - 23 Jul 2016

Cited by 5 | Viewed by 5660

Abstract

Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, [...] Read more.

Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Open AccessArticle

Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity

by Toshio Morikawa, Niichiro Kitagawa, Genzoh Tanabe, Kiyofumi Ninomiya, Shuhei Okugawa, Chiaki Motai, Iyori Kamei, Masayuki Yoshikawa, I-Jung Lee and Osamu Muraoka

Molecules 2016, 21(7), 930; https://doi.org/10.3390/molecules21070930 - 19 Jul 2016

Cited by 37 | Viewed by 8962

Abstract

A quantitative analytical method for five aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and five benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N [...] Read more.

A quantitative analytical method for five aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and five benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N-methylcoclaurine (8), coclaurine (9), and norjuziphine (10), identified as the constituents responsible for the melanogenesis inhibitory activity of the extracts of lotus flowers (the flower buds of Nelumbo nucifera), has been developed using liquid chromatography-mass spectrometry. The optimum conditions for separation and detection of these 10 alkaloids were achieved on a πNAP column, a reversed-phase column with naphthylethyl group-bonded silica packing material, with CH₃CN–0.2% aqueous acetic acid as the mobile phase and using mass spectrometry equipped with a positive-mode electrospray ionization source. According to the protocol established, distributions of these 10 alkaloids in the petal, receptacle, and stamen parts, which were separated from the whole flower, were examined. As expected, excellent correlations were observed between the total alkaloid content and melanogenesis inhibitory activity. Among the active alkaloids, nornuciferine (2) was found to give a carbamate salt (2′′) via formation of an unstable carbamic acid (2′) by absorption of carbon dioxide from the air. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Open AccessArticle

The Interference of Selected Cytotoxic Alkaloids with the Cytoskeleton: An Insight into Their Modes of Action

by Xiaojuan Wang, Mine Tanaka, Sonja Krstin, Herbenya Silva Peixoto and Michael Wink

Molecules 2016, 21(7), 906; https://doi.org/10.3390/molecules21070906 - 12 Jul 2016

Cited by 30 | Viewed by 7102

Abstract

Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine), which are known to affect neuroreceptors, protein biosynthesis and nucleic [...] Read more.

Alkaloids, the largest group among the nitrogen-containing secondary metabolites of plants, usually interact with several molecular targets. In this study, we provide evidence that six cytotoxic alkaloids (sanguinarine, chelerythrine, chelidonine, noscapine, protopine, homoharringtonine), which are known to affect neuroreceptors, protein biosynthesis and nucleic acids, also interact with the cellular cytoskeleton, such as microtubules and actin filaments, as well. Sanguinarine, chelerythrine and chelidonine depolymerized the microtubule network in living cancer cells (Hela cells and human osteosarcoma U2OS cells) and inhibited tubulin polymerization in vitro with IC₅₀ values of 48.41 ± 3.73, 206.39 ± 4.20 and 34.51 ± 9.47 μM, respectively. However, sanguinarine and chelerythrine did not arrest the cell cycle while 2.5 μM chelidonine arrested the cell cycle in the G₂/M phase with 88.27% ± 0.99% of the cells in this phase. Noscapine and protopine apparently affected microtubule structures in living cells without affecting tubulin polymerization in vitro, which led to cell cycle arrest in the G2/M phase, promoting this cell population to 73.42% ± 8.31% and 54.35% ± 11.26% at a concentration of 80 μM and 250.9 μM, respectively. Homoharringtonine did not show any effects on microtubules and cell cycle, while the known microtubule-stabilizing agent paclitaxel was found to inhibit tubulin polymerization in the presence of MAPs in vitro with an IC₅₀ value of 38.19 ± 3.33 μM. Concerning actin filaments, sanguinarine, chelerythrine and chelidonine exhibited a certain effect on the cellular actin filament network by reducing the mass of actin filaments. The interactions of these cytotoxic alkaloids with microtubules and actin filaments present new insights into their molecular modes of action. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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935 KiB

Open AccessCommunication

Cytotoxic Alkaloids from the Stem of Xylopia laevigata

by Leociley R. A. Menezes, Cinara O. D´Sousa Costa, Ana Carolina B. da C. Rodrigues, Felipe R. do E. Santo, Angelita Nepel, Lívia M. Dutra, Felipe M. A. Silva, Milena B. P. Soares, Andersson Barison, Emmanoel V. Costa and Daniel P. Bezerra

Molecules 2016, 21(7), 890; https://doi.org/10.3390/molecules21070890 - 08 Jul 2016

Cited by 31 | Viewed by 6842

Abstract

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (−)-roemerine, (+)-anonaine, [...] Read more.

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (−)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (−)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (−)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G₂/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Review

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1465 KiB

Open AccessReview

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

by Zeina Habli, Georgio Toumieh, Maamoun Fatfat, Omar Nasser Rahal and Hala Gali-Muhtasib

Molecules 2017, 22(2), 250; https://doi.org/10.3390/molecules22020250 - 08 Feb 2017

Cited by 98 | Viewed by 9184

Abstract

Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an [...] Read more.

Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Open AccessReview

¹³C-NMR Spectral Data of Alkaloids Isolated from Psychotria Species (Rubiaceae)

by Almir Ribeiro de Carvalho Junior, Ivo Jose Curcino Vieira, Mario Geraldo de Carvalho, Raimundo Braz-Filho, Mary Anne S. Lima, Rafaela Oliveira Ferreira, Edmilson José Maria and Daniela Barros de Oliveira

Molecules 2017, 22(1), 103; https://doi.org/10.3390/molecules22010103 - 11 Jan 2017

Cited by 9 | Viewed by 6074

Abstract

The genus Psychotria (Rubiaceae) comprises more than 2000 species, mainly found in tropical and subtropical forests. Several studies have been conducted concerning their chemical compositions, showing that this genus is a potential source of alkaloids. At least 70 indole alkaloids have been identified [...] Read more.

The genus Psychotria (Rubiaceae) comprises more than 2000 species, mainly found in tropical and subtropical forests. Several studies have been conducted concerning their chemical compositions, showing that this genus is a potential source of alkaloids. At least 70 indole alkaloids have been identified from this genus so far. This review aimed to compile ¹³C-NMR data of alkaloids isolated from the genus Psychotria as well as describe the main spectral features of different skeletons. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Open AccessReview

Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review

by Md Toufiqur Rahman, Veera V. N. Phani Babu Tiruveedhula and James M. Cook

Molecules 2016, 21(11), 1525; https://doi.org/10.3390/molecules21111525 - 14 Nov 2016

Cited by 42 | Viewed by 10912

Abstract

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of [...] Read more.

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family. The monomeric units belong to the sarpagine, ajmaline, macroline, vobasine, and pleiocarpamine series. An up-to-date discussion of their isolation, characterization, biological activity as well as approaches to their partial and total synthesis by means of both synthetic and biosynthetic strategies are presented. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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Open AccessReview

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

by Neill Kim, Olga Estrada, Benjamin Chavez, Charles Stewart and John C. D’Auria

Molecules 2016, 21(11), 1510; https://doi.org/10.3390/molecules21111510 - 11 Nov 2016

Cited by 50 | Viewed by 14615

Abstract

The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may [...] Read more.

The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring to their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. In addition, modern approaches to producing some pharmaceutically important tropanes via metabolic engineering endeavors are discussed. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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3145 KiB

Open AccessReview

Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

by Shinji Kishimoto, Michio Sato, Yuta Tsunematsu and Kenji Watanabe

Molecules 2016, 21(8), 1078; https://doi.org/10.3390/molecules21081078 - 18 Aug 2016

Cited by 44 | Viewed by 16535

Abstract

Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants [...] Read more.

Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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