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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 -
Biomolecules Nov 2021Plants produce a large variety of low-molecular-weight and specialized secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active... (Review)
Review
Plants produce a large variety of low-molecular-weight and specialized secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used in the pharmaceutical industry. Although alkaloid chemistry has been intensively investigated, characterization of alkaloid biosynthesis, including biosynthetic enzyme genes and their regulation, especially the transcription factors involved, has been relatively delayed, since only a limited number of plant species produce these specific types of alkaloids in a tissue/cell-specific or developmental-specific manner. Recent advances in molecular biology technologies, such as RNA sequencing, co-expression analysis of transcripts and metabolites, and functional characterization of genes using recombinant technology and cutting-edge technology for metabolite identification, have enabled a more detailed characterization of alkaloid pathways. Thus, transcriptional regulation of alkaloid biosynthesis by transcription factors, such as basic helix-loop-helix (bHLH), APETALA2/ethylene-responsive factor (AP2/ERF), and WRKY, is well elucidated. In addition, jasmonate signaling, an important cue in alkaloid biosynthesis, and its cascade, interaction of transcription factors, and post-transcriptional regulation are also characterized and show cell/tissue-specific or developmental regulation. Furthermore, current sequencing technology provides more information on the genome structure of alkaloid-producing plants with large and complex genomes, for genome-wide characterization. Based on the latest information, we discuss the application of transcription factors in alkaloid engineering.
Topics: Alkaloids; Gene Expression Regulation, Plant; Oxylipins; Transcription Factors
PubMed: 34827717
DOI: 10.3390/biom11111719 -
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 -
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 -
Molecules (Basel, Switzerland) Jun 2023Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant , is the only bisbenzylisoquinoline alkaloid approved for human use and has been... (Review)
Review
Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant , is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we aimed to describe the pharmacological properties and mechanisms of cepharanthine, mainly including antitumor, anti-inflammatory, anti-pathogen activities, inhibition of bone resorption, treatment of alopecia, treatment of snake bite, and other activities. At the same time, we analyzed and summarized the potential antiviral mechanism of cepharanthine and concluded that one of the most important anti-viral mechanisms of cepharanthine may be the stability of plasma membrane fluidity. Additionally, we explained its safety and bioavailability, which provides evidence for cepharanthine as a potential drug for the treatment of a variety of diseases. Finally, we further discuss the potential new clinical applications of cepharanthine and provide direction for its future development.
Topics: Humans; COVID-19; SARS-CoV-2; Benzylisoquinolines; Alkaloids; Antiviral Agents
PubMed: 37446681
DOI: 10.3390/molecules28135019 -
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 -
Molecules (Basel, Switzerland) Sep 2021spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of plants have been used for the treatment of ailments... (Review)
Review
spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17-45 spp., alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied alkaloids are cyclopamine (), veratramine (), isorubijervine (), muldamine (), cycloposine (), and veratrosine (). Recent inspection of the ethanolic extract from root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine () etioline (), tetrahydrojervine () dihydrojervine (), 22-keto-26-aminocholesterol (). For each alkaloid identified or proposed in , this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.
Topics: Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Biological Products; Humans; Neoplasms; Veratrum
PubMed: 34641477
DOI: 10.3390/molecules26195934 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2021Piperine (PIP) is an alkaloid present in several species of piper, mainly Piper nigrum Linn. and P. longum, among other species. The present article provides a... (Review)
Review
Piperine (PIP) is an alkaloid present in several species of piper, mainly Piper nigrum Linn. and P. longum, among other species. The present article provides a comprehensive review of PIP research in the last years concerning its chemical properties, synthesis, absorption, metabolism, bioavailability and toxicity. The reviewed PIP literature has shown many pharmacological properties, such as antidiabetic, antidiarrheal, antioxidant, antibacterial, and anti-parasitic activity of PIP. However, its low solubility and absorption make its application challenging. This review also includes advances in the development of nanosystems containing PIP, including liposomes, micelles, metal nanoparticles, nanofibers, polymeric nanoparticles, and solid-lipid nanoparticles. Finally, we discuss different in vitro and in vivo studies to evaluate the biological activity of this drug, as well as some methods for the synthesis of nanosystems and their physical characteristics.
Topics: Alkaloids; Animals; Benzodioxoles; Biological Availability; Humans; Liposomes; Micelles; Nanoparticles; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Solubility
PubMed: 33151173
DOI: 10.2478/acph-2021-0015 -
Molecules (Basel, Switzerland) Jul 2015This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this... (Review)
Review
This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion.
Topics: Alkaloids; Anthraquinones; Iridoids; Rubiaceae
PubMed: 26205062
DOI: 10.3390/molecules200713422