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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 -
Molecules (Basel, Switzerland) Jul 2023Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or... (Review)
Review
Cancer is a neoplastic disease that remains a global challenge with a reported prevalence that is increasing annually. Though existing drugs can be applied as single or combined therapies for managing this pathology, their concomitant adverse effects in human applications have led to the need to continually screen natural products for effective and alternative anticancer bioactive principles. Alkaloids are chemical molecules that, due to their structural diversity, constitute a reserve for the discovery of lead compounds with interesting pharmacological activities. Several in vitro studies and a few in vivo findings have documented various cytotoxic and antiproliferative properties of alkaloids. This review describes chaetocochin J, neopapillarine, coclaurine, reflexin A, 3,10-dibromofascaplysin and neferine, which belong to different alkaloid classes with antineoplastic properties and have been identified recently from plants. Despite their low solubility and bioavailability, plant-derived alkaloids have viable prospects as sources of viable lead antitumor agents. This potential can be achieved if more research on these chemical compounds is directed toward investigating ways of improving their delivery in an active form close to target cells, preferably with no effect on neighboring normal tissues.
Topics: Humans; Alkaloids; Antineoplastic Agents; Neoplasms; Plant Extracts
PubMed: 37513450
DOI: 10.3390/molecules28145578 -
Toxins Apr 2015The ergot alkaloid biosynthesis system has become an excellent model to study evolutionary diversification of specialized (secondary) metabolites. This is a very diverse... (Review)
Review
The ergot alkaloid biosynthesis system has become an excellent model to study evolutionary diversification of specialized (secondary) metabolites. This is a very diverse class of alkaloids with various neurotropic activities, produced by fungi in several orders of the phylum Ascomycota, including plant pathogens and protective plant symbionts in the family Clavicipitaceae. Results of comparative genomics and phylogenomic analyses reveal multiple examples of three evolutionary processes that have generated ergot-alkaloid diversity: gene gains, gene losses, and gene sequence changes that have led to altered substrates or product specificities of the enzymes that they encode (neofunctionalization). The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization. Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids. Genetic alterations associated with interspecific hybrids of Epichloë species suggest that such variation is also selectively favored. The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine.
Topics: Ergot Alkaloids; Genetic Loci; Genetic Variation; Genomics; Humans; Phylogeny; Synteny
PubMed: 25875294
DOI: 10.3390/toxins7041273 -
Molecules (Basel, Switzerland) Aug 2016Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities.... (Review)
Review
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.
Topics: Alkaloids; Bacteria; Biosynthetic Pathways; Fungi; Metabolic Engineering; Molecular Structure
PubMed: 27548127
DOI: 10.3390/molecules21081078 -
Natural Product Reports Jan 2021Alkaloids from plants are characterised by structural diversity and bioactivity, and maintain a privileged position in both modern and traditional medicines. In recent... (Review)
Review
Alkaloids from plants are characterised by structural diversity and bioactivity, and maintain a privileged position in both modern and traditional medicines. In recent years, there have been significant advances in elucidating the biosynthetic origins of plant alkaloids. In this review, I will describe the progress made in determining the metabolic origins of the so-called true alkaloids, specialised metabolites derived from amino acids containing a nitrogen heterocycle. By identifying key biosynthetic steps that feature in the majority of pathways, I highlight the key roles played by modifications to primary metabolism, iminium reactivity and spontaneous reactions in the molecular and evolutionary origins of these pathways.
Topics: Aldehydes; Alkaloids; Amines; Amino Acids; Biosynthetic Pathways; Enzymes; Evolution, Molecular; Plant Proteins; Plants
PubMed: 32745157
DOI: 10.1039/d0np00031k -
Current Opinion in Chemical Biology Apr 2016Metabolic pathways leading to benzylisoquinoline and monoterpene indole alkaloids in plants are revealing remarkable new reactions. Understanding of the enzymes involved... (Review)
Review
Metabolic pathways leading to benzylisoquinoline and monoterpene indole alkaloids in plants are revealing remarkable new reactions. Understanding of the enzymes involved in alkaloid biosynthesis provides access to a variety of applications in biocatalysis and bioengineering. In chemo-enzymatic settings, plant biocatalysts can transform medically important scaffolds. Additionally, synthetic biologists are taking alkaloid pathways as templates to assemble pathways in microorganisms that are tailored to the needs of medicinal chemistry. In light of these many recent discoveries, it is expected that plants will continue to be a source of novel biocatalysts for the foreseeable future.
Topics: Alkaloids; Biocatalysis; Enzymes; Plant Proteins; Plants
PubMed: 26773811
DOI: 10.1016/j.cbpa.2015.12.006 -
The Plant Genome Jun 2022The tomato (Solanum spp.) clade of Solanaceae features a unique assortment of cholesterol-derived steroidal alkaloids. However, little quantitative data exists reporting...
The tomato (Solanum spp.) clade of Solanaceae features a unique assortment of cholesterol-derived steroidal alkaloids. However, little quantitative data exists reporting the profile and concentration of these alkaloids across diverse fruit germplasm. To address the lack of knowledge regarding the chemical diversity, concentration, and genetic architecture controlling tomato steroidal alkaloids, we quantitatively profiled and genotyped two tomato populations representing diversity in the red-fruited clade. We grew 107 genetically diverse fresh market, processing, landrace, and wild tomato in multiple environments. Nine steroidal alkaloid groups were quantified using ultra-high performance liquid chromatography tandem mass spectrometry. The diversity panel and a biparental population segregating for high alpha-tomatine were genotyped to identify and validate quantitative trait loci (QTL) associated with steroidal alkaloids. Landraces and wild material exhibited higher alkaloid concentrations and more chemical diversity. Average total content of steroidal alkaloids, often dominated by lycoperoside F/G/esculeoside A, ranged from 1.9 to 23.3 mg 100 g fresh wt. across accessions. Landrace and wild cherry accessions distinctly clustered based on elevated concentrations of early or late-pathway steroidal alkaloids. Significant correlations were observed among alkaloids from the early and late parts of the biosynthetic pathway in a species-dependent manner. A QTL controlling multiple, early steroidal alkaloid pathway intermediates on chromosome 3 was identified by genome-wide association studies (GWAS) and validated in a backcross population. Overall, tomato steroidal alkaloids are diverse in the red-fruited clade and their biosynthesis is regulated in a coordinated manner.
Topics: Alkaloids; Fruit; Genome-Wide Association Study; Solanum lycopersicum; Quantitative Trait Loci
PubMed: 35184399
DOI: 10.1002/tpg2.20192 -
Toxins Feb 2022Plants are the cradle of the traditional medicine system, assuaging human or animal diseases, and promoting health for thousands of years. However, many plant-derived... (Review)
Review
Plants are the cradle of the traditional medicine system, assuaging human or animal diseases, and promoting health for thousands of years. However, many plant-derived medicines contain toxic alkaloids of varying degrees of toxicity that pose a direct or indirect threat to human and animal health through accidental ingestion, misuse of plant materials, or through the food chain. Thus, rapid, easy, and sensitive methods are needed to effectively screen these toxic alkaloids to guarantee the safety of plant-derived medicines. Antibodies, due to their inherent specificity and high affinity, have been used as a variety of analytical tools and techniques. This review describes the antigen synthesis and antibody preparation of the common toxic alkaloids in plant-derived medicines and discusses the advances of antibody-based immunoassays in the screening and detection of toxic alkaloids in plants or other related matrices. Finally, the limitations and prospects of immunoassays for toxic alkaloids are discussed.
Topics: Alkaloids; Animals; Immunoassay; Medicine, Traditional; Plants, Toxic
PubMed: 35324662
DOI: 10.3390/toxins14030165 -
Toxins Jan 2016Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom... (Review)
Review
Ants (Formicidae) represent a taxonomically diverse group of hymenopterans with over 13,000 extant species, the majority of which inject or spray secretions from a venom gland. The evolutionary success of ants is mostly due to their unique eusociality that has permitted them to develop complex collaborative strategies, partly involving their venom secretions, to defend their nest against predators, microbial pathogens, ant competitors, and to hunt prey. Activities of ant venom include paralytic, cytolytic, haemolytic, allergenic, pro-inflammatory, insecticidal, antimicrobial, and pain-producing pharmacologic activities, while non-toxic functions include roles in chemical communication involving trail and sex pheromones, deterrents, and aggregators. While these diverse activities in ant venoms have until now been largely understudied due to the small venom yield from ants, modern analytical and venomic techniques are beginning to reveal the diversity of toxin structure and function. As such, ant venoms are distinct from other venomous animals, not only rich in linear, dimeric and disulfide-bonded peptides and bioactive proteins, but also other volatile and non-volatile compounds such as alkaloids and hydrocarbons. The present review details the unique structures and pharmacologies of known ant venom proteinaceous and alkaloidal toxins and their potential as a source of novel bioinsecticides and therapeutic agents.
Topics: Alkaloids; Animals; Ant Venoms; Ants; Humans; Insect Proteins; Peptides
PubMed: 26805882
DOI: 10.3390/toxins8010030 -
Molecules (Basel, Switzerland) Jun 2022Thirty-three benzophenanthridine alkaloid derivatives (- and -) were synthesized, and their cytotoxic activities against two leukemia cell lines (Jurkat Clone E6-1 and...
Thirty-three benzophenanthridine alkaloid derivatives (- and -) were synthesized, and their cytotoxic activities against two leukemia cell lines (Jurkat Clone E6-1 and THP-1) were evaluated in vitro using a Cell Counting Kit-8 (CCK-8) assay. Nine of these derivatives (-, and -) with IC values in the range of 0.18-7.94 μM showed significant inhibitory effects on the proliferation of both cancer cell lines. Analysis of the primary structure-activity relationships revealed that different substituent groups at the C-6 position might have an effect on the antileukemia activity of the corresponding compounds. In addition, the groups at the C-7 and C-8 positions could influence the antileukemia activity. Among these compounds, showed the strongest in vitro antiproliferative activity against Jurkat Clone E6-1 and THP-1 cells with good IC values (0.52 ± 0.03 μM and 0.48 ± 0.03 μM, respectively), slightly induced apoptosis, and arrested the cell-cycle, all of which suggests that compound may represent a potentially useful start point to undergo further optimization toward a lead compound.
Topics: Alkaloids; Antineoplastic Agents; Apoptosis; Benzophenanthridines; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Molecular Structure; Structure-Activity Relationship
PubMed: 35745057
DOI: 10.3390/molecules27123934