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Molecules (Basel, Switzerland) Jun 2021Phytochemicals belonging to the group of alkaloids are signature specialized metabolites endowed with countless biological activities. Plants are armored with these... (Review)
Review
Phytochemicals belonging to the group of alkaloids are signature specialized metabolites endowed with countless biological activities. Plants are armored with these naturally produced nitrogenous compounds to combat numerous challenging environmental stress conditions. Traditional and modern healthcare systems have harnessed the potential of these organic compounds for the treatment of many ailments. Various chemical entities (functional groups) attached to the central moiety are responsible for their diverse range of biological properties. The development of the characterization of these plant metabolites and the enzymes involved in their biosynthesis is of an utmost priority to deliver enhanced advantages in terms of biological properties and productivity. Further, the incorporation of whole/partial metabolic pathways in the heterologous system and/or the overexpression of biosynthetic steps in homologous systems have both become alternative and lucrative methods over chemical synthesis in recent times. Moreover, in-depth research on alkaloid biosynthetic pathways has revealed numerous chemical modifications that occur during alkaloidal conversions. These chemical reactions involve glycosylation, acylation, reduction, oxidation, and methylation steps, and they are usually responsible for conferring the biological activities possessed by alkaloids. In this review, we aim to discuss the alkaloidal group of plant specialized metabolites and their brief classification covering major categories. We also emphasize the diversity in the basic structures of plant alkaloids arising through enzymatically catalyzed structural modifications in certain plant species, as well as their emerging diverse biological activities. The role of alkaloids in plant defense and their mechanisms of action are also briefly discussed. Moreover, the commercial utilization of plant alkaloids in the marketplace displaying various applications has been enumerated.
Topics: Acylation; Alkaloids; Biosynthetic Pathways; Glycosylation; Methylation; Molecular Structure; Oxidation-Reduction; Phytochemicals; Plant Physiological Phenomena; Plants
PubMed: 34204857
DOI: 10.3390/molecules26113374 -
The Alkaloids. Chemistry and Biology 2017Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts... (Review)
Review
Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.
Topics: Animals; Antineoplastic Agents, Phytogenic; Harringtonines; Humans
PubMed: 28838429
DOI: 10.1016/bs.alkal.2017.07.001 -
Molecules (Basel, Switzerland) Mar 2023The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline... (Review)
Review
The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterase in smooth muscles, and it has been observed to increase intracellular levels of cAMP and cGMP. It induces coronary, cerebral, and pulmonary artery dilatation and helps to lower cerebral vascular resistance and enhance cerebral blood flow. Current pharmacological research has revealed that papaverine demonstrates a variety of biological activities, including activity against erectile dysfunction, postoperative vasospasms, and pulmonary vasoconstriction, as well as antiviral, cardioprotective, anti-inflammatory, anticancer, neuroprotective, and gestational actions. It was recently demonstrated that papaverine has the potential to control SARS-CoV-2 by preventing its cytopathic effect. These experiments were carried out both in vitro and in vivo and require an extensive understanding of the mechanisms of action. With its multiple mechanisms, papaverine can be considered as a natural compound that is used to develop therapeutic drugs. To validate its applications, additional research is required into its precise therapeutic mechanisms as well as its acute and chronic toxicities. Therefore, the goal of this review is to discuss the major studies and reported clinical studies looking into the pharmacological effects of papaverine and the mechanisms of action underneath these effects. Additionally, it is recommended to conduct further research via significant pharmacodynamic and pharmacokinetic studies.
Topics: Humans; Papaverine; Opium; COVID-19; SARS-CoV-2; Alkaloids; Benzylisoquinolines
PubMed: 37049912
DOI: 10.3390/molecules28073149 -
Nutrients Jul 2020Caffeine is a naturally occurring plant alkaloid and is found in plant constituents such as coffee and cocoa beans, tea leaves, guarana berries and the kola nut [...].
Caffeine is a naturally occurring plant alkaloid and is found in plant constituents such as coffee and cocoa beans, tea leaves, guarana berries and the kola nut [...].
Topics: Alkaloids; Athletes; Cacao; Caffeine; Coffee; Diet; Doping in Sports; Fruit; Humans; Paullinia; Performance-Enhancing Substances; Plant Leaves; Tea
PubMed: 32707772
DOI: 10.3390/nu12082167 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Oct 2020Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S... (Review)
Review
Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Topics: Alkaloids; Catalysis; Enzymes; Research; Tetrahydroisoquinolines
PubMed: 33169566
DOI: 10.13345/j.cjb.200064 -
Molecular Diversity May 2015Nature is full of dimeric alkaloids of various types from many plant families, some of them with interesting biological properties. However, dimeric Cinchona alkaloids... (Review)
Review
Nature is full of dimeric alkaloids of various types from many plant families, some of them with interesting biological properties. However, dimeric Cinchona alkaloids were not isolated from any species but were products of designed partial chemical synthesis. Although the Cinchona bark is amongst the sources of oldest efficient medicines, the synthetic dimers found most use in the field of asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and their structure and applications are outlined. Various synthetic routes exploit reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and quinoline rings, as well as 3-vinyl group. This availability of reactive sites, in combination with a plethora of linker molecules, contributes to the diversity of the products obtained.
Topics: Cinchona Alkaloids; Molecular Structure
PubMed: 25586655
DOI: 10.1007/s11030-014-9563-1 -
BMC Research Notes Sep 2021Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In...
OBJECTIVE
Papaver decaisnei Hochst. & Steud. Ex Elkan and Papaver glaucum Boiss. & Hausskn. growing wild in Northern Iraq have been historically used for medicinal purposes. In this study, both species were evaluated for their alkaloid content and antimicrobial activities.
RESULTS
Alkaloids were extracted and isolated by preparative thin-layer chromatography (TLC). Identification was carried out by comparing spectral data (UV and H-NMR) and TLC Rf values with those of authentic samples. Two alkaloids, proapaorphine-type mecambrine and aporphine-type roemerine were isolated from P. decaisnei. Two benzylisoquinoline type alkaloids papaverine (major alkaloid) and palaudine as well as aporphine-type N-methylasimilobine have been obtained in P. glaucum. Both P. glaucum and P. decaisnei extracts revealed strong antimicrobial activity on Pseudomonas aeruginosa ATCC 27853 and Enterococcus faecalis ATCC 29212. Collectively these results indicate that P. glaucum and P. decaisnei are promising sources of alkaloids that could further be investigated for medicinal purposes.
Topics: Alkaloids; Anti-Infective Agents; Chromatography, Thin Layer; Papaver; Plant Extracts
PubMed: 34496958
DOI: 10.1186/s13104-021-05762-x -
Molecules (Basel, Switzerland) Feb 2022The absolute stereochemistry of the marine alkaloid ()-()-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from...
The absolute stereochemistry of the marine alkaloid ()-()-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH.
Topics: Alkaloids; Chemistry Techniques, Synthetic; Combinatorial Chemistry Techniques; Molecular Structure
PubMed: 35209136
DOI: 10.3390/molecules27041338 -
Molecules (Basel, Switzerland) Nov 2016The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties... (Review)
Review
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.
Topics: Alkaloids; Biosynthetic Pathways; Metabolic Engineering; Plant Extracts; Secondary Metabolism; Tropanes
PubMed: 27845728
DOI: 10.3390/molecules21111510 -
International Review of Cell and... 2013Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are... (Review)
Review
Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.
Topics: Alkaloids; Plants; Transcription Factors
PubMed: 23890386
DOI: 10.1016/B978-0-12-407695-2.00008-1