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Food Chemistry Jul 2024Pyrrolizidine alkaloids (PAs) in food and natural preparations have received widespread attention due to their hepatotoxicity, genotoxicity, and embryotoxicity. Mass... (Review)
Review
Pyrrolizidine alkaloids (PAs) in food and natural preparations have received widespread attention due to their hepatotoxicity, genotoxicity, and embryotoxicity. Mass spectrometry (MS), as a high resolution, high sensitive, and high throughput detection tool, has been the most commonly used technique for the determination of PAs. The continuous advancement of new technologies, methods, and strategies in the field of MS has contributed to the improvement of the analytical efficiency and methodological enhancement of PAs. This paper provides an overview of the structure, toxicity properties and commonly employed analytical methods, focusing on the concepts, advances, and novel techniques and applications of MS-based methods for the analysis of PAs. Additionally, the remaining challenges, future perspectives, and trends for PA detection are discussed. This review provides a reference for toxicological studies of PAs, content monitoring, and the establishment of quality control and safety standards for herbal and food products.
Topics: Pyrrolizidine Alkaloids; Mass Spectrometry; Food
PubMed: 38422865
DOI: 10.1016/j.foodchem.2024.138748 -
Phytochemistry Dec 2023Crinum x powellii 'Album' belongs to the Amaryllidaceae medicinal plant family that produces a range of structurally diverse alkaloids with potential therapeutic...
Crinum x powellii 'Album' belongs to the Amaryllidaceae medicinal plant family that produces a range of structurally diverse alkaloids with potential therapeutic properties. The optimal conditions for in vitro tissue growth, morphogenesis, and alkaloid biosynthesis remain unclear. Auxin and light play critical roles in regulating plant growth, development, and alkaloid biosynthesis in several Amaryllidaceae plants. Here, we have succeeded in showing, for the first time, that the combination of auxin and light significantly influence C. x powellii "Album" in vitro tissue growth, survival, and morphogenesis compared to individual treatments. Furthermore, this combination also upregulates the expression of alkaloid biosynthetic genes and led to an increase in the content of certain alkaloids, suggesting a positive impact on the defense and therapeutic potential of the calli. Our findings provide insights into the regulation of genes involved in alkaloid biosynthesis in C. x powellii "Album" callus and underline the potential of auxin and light as tools for enhancing their production in plants. This study provides a foundation for further exploration of C. x powellii "Album" calli as a sustainable source of bioactive alkaloids for pharmaceutical and agricultural applications. Furthermore, this study paves the way to the discovery of the biosynthetic pathway of specialized metabolites from C. x powellii "Album", such as cherylline and lycorine.
Topics: Crinum; Indoleacetic Acids; Amaryllidaceae Alkaloids; Alkaloids; Plant Extracts; Morphogenesis
PubMed: 37820888
DOI: 10.1016/j.phytochem.2023.113883 -
European Journal of Medicinal Chemistry Nov 2023Since the first natural carbazole alkaloid, murrayanine, was isolated from Mwraya Spreng, carbazole alkaloid derivatives have been widely concerned for their anti-tumor,... (Review)
Review
Since the first natural carbazole alkaloid, murrayanine, was isolated from Mwraya Spreng, carbazole alkaloid derivatives have been widely concerned for their anti-tumor, anti-viral and anti-bacterial activities. In recent decades, a growing body of data suggest that carbazole alkaloids and their derivatives have different biological activities. This is the first comprehensive description of the antifungal and antibacterial activities of carbazole alkaloids in the past decade (2012-2022), including natural and partially synthesized carbazole alkaloids in the past decade. Finally, the challenges and problems faced by this kind of alkaloids are summarized. This paper will be helpful for further exploration of this kind of alkaloids.
Topics: Alkaloids; Anti-Bacterial Agents; Antifungal Agents; Antineoplastic Agents; Carbazoles; Molecular Structure
PubMed: 37467619
DOI: 10.1016/j.ejmech.2023.115627 -
Molecules (Basel, Switzerland) Jul 2023The natural alkaloid gramine has attracted significant attention in both academic and industrial circles because of its potential and diverse biological activities,... (Review)
Review
The natural alkaloid gramine has attracted significant attention in both academic and industrial circles because of its potential and diverse biological activities, including antiviral, antibacterial, antifungal, anti-inflammatory and antitumor activities; application in therapy for Alzheimer's disease; serotonin-receptor-related activity; insecticidal activity; and application as an algicide. In this review, we focus on the research advances that have been made for gramine-based molecules since their discovery, providing key information on their extraction and separation, chemical synthesis and diverse biological activities. Data regarding their mechanisms of action are also presented. This comprehensive and critical review will serve as a guide for developing more drug candidates based on gramine skeletons.
Topics: Indole Alkaloids; Alkaloids
PubMed: 37570664
DOI: 10.3390/molecules28155695 -
Natural Product Reports Jan 2024Covering: up to 2023Huperzine alkaloids are a group of natural products belonging to the alkaloids family. The representative member huperzine A has a unique structure... (Review)
Review
Covering: up to 2023Huperzine alkaloids are a group of natural products belonging to the alkaloids family. The representative member huperzine A has a unique structure and exhibits potent inhibitory activity against acetylcholine esterase (AChE). This subfamily of alkaloids provides a great opportunity for developing synthetic methodologies and asymmetric synthesis. The efforts towards the synthesis of huperzine A have cultivated dozens of total syntheses and a rich body of new chemistry. Impressive progress has also been made in the synthesis of other huperzine alkaloids. The total syntheses of huperzines B, U, O, Q and R, structure reassignment and total syntheses of huperzines K, M and N have been reported in the past decade. This review focuses on the synthetic organic chemistry and the biosynthesis and medicinal chemistry of huperzines are also covered briefly.
Topics: Molecular Structure; Lycopodium; Alkaloids; Sesquiterpenes
PubMed: 37818549
DOI: 10.1039/d3np00029j -
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 -
Nature Dec 2023Plants synthesize numerous alkaloids that mimic animal neurotransmitters. The diversity of alkaloid structures is achieved through the generation and tailoring of unique...
Plants synthesize numerous alkaloids that mimic animal neurotransmitters. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known. By studying highly coordinated, tissue-specific gene expression in plants that produce neuroactive Lycopodium alkaloids, we identified an unexpected enzyme class for alkaloid biosynthesis: neofunctionalized α-carbonic anhydrases (CAHs). We show that three CAH-like (CAL) proteins are required in the biosynthetic route to a key precursor of the Lycopodium alkaloids by catalysing a stereospecific Mannich-like condensation and subsequent bicyclic scaffold generation. Also, we describe a series of scaffold tailoring steps that generate the optimized acetylcholinesterase inhibition activity of huperzine A. Our findings suggest a broader involvement of CAH-like enzymes in specialized metabolism and demonstrate how successive scaffold tailoring can drive potency against a neurological protein target.
Topics: Animals; Acetylcholinesterase; Alkaloids; Carbonic Anhydrases; Cholinesterase Inhibitors; Gene Expression Regulation, Plant; Models, Neurological; Neurotransmitter Agents; Plants; Sesquiterpenes; Lycopodium
PubMed: 37938780
DOI: 10.1038/s41586-023-06716-y -
Journal of the American Chemical Society Oct 2023A concise and enantioselective total synthesis of the alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS)...
A concise and enantioselective total synthesis of the alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a synthesis of the -6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji-Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.
Topics: Cyclization; Alkenes; Veratrum Alkaloids; Stereoisomerism
PubMed: 37782691
DOI: 10.1021/jacs.3c09085 -
Journal of Medicinal Chemistry Aug 2023Induction of ferroptosis emerges as an effective method for cancer treatment. With massive efforts to elucidate the ferroptosis mechanism, the development of new...
Induction of ferroptosis emerges as an effective method for cancer treatment. With massive efforts to elucidate the ferroptosis mechanism, the development of new ferroptosis inducers proceeds rather slowly, with only a few small molecules identified. Herein, we report our discovery of marine alkaloid lepadins E and H as a new class of ferroptosis inducers. Our in vitro studies show that lepadins E and H exhibit significant cytotoxicity, promote p53 expression, increase ROS production and lipid peroxides, reduce SLC7A11 and GPX4 levels, and upregulate ACSL4 expression, all of which consistently support induction of ferroptosis through the classical p53-SLC7A11-GPX4 pathway. Our animal model study of lepadin H confirms its in vivo antitumor efficacy with negligible toxicity to normal organs. This work elucidates the mode of action of lepadins (E and H) and verifies their in vivo efficacy as a new class of ferroptosis inducers for anticancer therapy with translational potential.
Topics: Animals; Alkaloids; Antineoplastic Agents; Ferroptosis; Neoplasms; Tumor Suppressor Protein p53
PubMed: 37578947
DOI: 10.1021/acs.jmedchem.3c00659 -
Toxins Jul 2023Venoms produced by arthropods act as chemical weapons to paralyze prey or deter competitors. The utilization of venom is an essential feature in the biology and ecology... (Review)
Review
Venoms produced by arthropods act as chemical weapons to paralyze prey or deter competitors. The utilization of venom is an essential feature in the biology and ecology of venomous arthropods. fire ants (Hymenoptera: Formicidae) are medically important venomous ants. They have acquired different patterns of venom use to maximize their competitive advantages rendered by the venom when facing different challenges. The major components of fire ant venom are piperidine alkaloids, which have strong insecticidal and antibiotic activities. The alkaloids protect fire ants from pathogens over the course of their lives and can be used to defend them from predators and competitors. They are also utilized by some of the fire ants' natural enemies, such as phorid flies to locate host ants. Collectively, these ants' diverse alkaloid compositions and functions have ecological significance for their survival, successful invasion, and rapid range expansion. The venom alkaloids with powerful biological activities may have played an important role in shaping the assembly of communities in both native and introduced ranges.
Topics: Animals; Ant Venoms; Arthropod Venoms; Ants; Diptera; Alkaloids
PubMed: 37505709
DOI: 10.3390/toxins15070439