Alkaloids produced by endophytic fungi: a review

In recent years, a number of alkaloids have been discovered from endophytic fungi in plants, which exhibited excellent biological properties such as antimicrobial, insecticidal, cytotoxic, and anticancer activities. This review mainly deals with the research progress on endophytic fungi for producing bioactive alkaloids such as quinoline and isoquinoline, amines and amides, indole derivatives, pyridines, and quinazolines. The biological activities and action mechanisms of these alkaloids from endophytic fungi are also introduced. Furthermore, the relationships between alkaloid-producing endophytes and their host plants, as well as their potential applications in the future are discussed.     

Advances in the Chemical and Biological Characterization of Amaryllidaceae Alkaloids and Natural Analogues Isolated in the Last Decade

Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and flavonoids content. Hundreds of alkaloids have been isolated until now and several scientific publications reported their sources, chemical structures, and biological activities. During the last decade, some unstudied Amaryllidaceae plants were the object of in-depth investigations to isolate and chemically and biologically characterize new and already known alkaloids as well as some analogues. This review describes the isolation and chemical and biological characterization of the Amaryllidaceae alkaloids, and their analogues obtained in the last decade, focusing the discussion on the new ones.     

Cannabinoids,Phenolics, Terpenes and Alkaloids of Cannabis

Cannabis sativa is one of the oldest medicinal plants in the world. It was introduced into western medicine during the early 19th century. It contains a complex mixture of secondary metabolites, including cannabinoids and non-cannabinoid-type constituents. More than 500 compounds have been reported from C. sativa, of which 125 cannabinoids have been isolated and/or identified as cannabinoids. Cannabinoids are C₂₁ terpeno-phenolic compounds specific to Cannabis. The non-cannabinoid constituents include: non-cannabinoid phenols, flavonoids, terpenes, alkaloids and others. This review discusses the chemistry of the cannabinoids and major non-cannabinoid constituents (terpenes, non-cannabinoid phenolics, and alkaloids) with special emphasis on their chemical structures, methods of isolation, and identification.     

Stereoselective Mannich Reactions in the Synthesis of Enantiopure Piperidine Alkaloids and Derivatives

Piperidine alkaloids are members of the alkaloid family that is characterized by the presence of a six-membered nitrogen-containing heterocycle. Piperidine alkaloids are found mainly in plants and often exhibit interesting biological and pharmacological activities. Despite the accumulation of these natural products in plants, relatively low quantities of alkaloids are produced in absolute terms and thus synthesis of alkaloids and derivatives thereof remains relevant to identify targets for drug discovery. Throughout the years, researchers have come up with a myriad of methods to synthesize piperidine derivatives. This review describes methods that employ stereoselective Mannich reactions to create the core of piperidine alkaloids. Asymmetric induction in the Mannich reaction has been achieved by a range of methods that have been divided into three conceptual approaches: (1) chiral pool-based (internal asymmetric induction), (2) chiral auxiliary-based (relayed asymmetric induction) and (3) asymmetric catalysis-based (external asymmetric induction). Of each approach, we describe the reaction mechanism and rationalize the stereochemical outcome of the Mannich products.     

Potentials of phyto-fabricated nanoparticles as ecofriendly agents for photocatalytic degradation of toxic dyes and waste water treatment,risk assessment and probable mechanism

Nanotechnology is a promising field and has diverse applications. Primarily, nanoparticles have been synthesized via chemical and physical methods. Dyes are synthetic organic compounds that are abundantly used in industries especially in textile industry. The use of these dyes is major contributors towards environmental pollution. Their hazardous nature raises great concerns in general public. Advancement in nanotechnology can efficiently help in mitigating this problem as nanoparticles can efficiently convert these harmful dyes into less harmful chemical byproducts through a process called Photocatalysis. Although, different approaches have been used for the synthesis of nanoparticles and their Photocatalytic activity but the most efficient approach is the green synthesis using different plants. This approach is environment-friendly and cost-effective. In order to reduce the toxic effects of synthetic dyes that pollutes the environment, it is important to look for such environmental friendly approaches and highlight the role of green nanotechnology in photocatalysis. In the present review paper, we for the first time have summarized the application of biogenic nanoparticles used as Photocatalytic agent in the degradation of different dyes such MB, MO and MR. We have presented a comprehensive review of chemistry/engineering approach of the technology along with mechanistic aspects. Furthermore, key applications of nanotechnology in Photocatalysis have been discussed along with futuristic insight.     

Acetylcholinesterase inhibitors from plants and fungi

This review describes 183 compounds obtained from plants and fungi which have been shown to inhibit acetylcholinesterase. The mechanism of action of cholinesterase, together with the binding sites, and, where this is known, the mode of action of inhibitors is described. The relative activities of the different compounds are recorded. The strongest inhibitors are generally alkaloids although some meroterpenoids from fungi have also been found to be active and display better selectivity.     

Natural Products and Their Derivatives against Human Herpesvirus Infection

Herpesviruses establish long-term latent infection for the life of the host and are known to cause numerous diseases. The prevalence of viral infection is significantly increased and causes a worldwide challenge in terms of health issues due to drug resistance. Prolonged treatment with conventional antiviral drugs is more likely to develop drug-resistant strains due to mutations of thymidine nucleoside kinase or DNA polymerase. Hence, the development of alternative treatments is clearly required. Natural products and their derivatives have played a significant role in treating herpesvirus infection rather than nucleoside analogs in drug-resistant strains with minimal undesirable effects and different mechanisms of action. Numerous plants, animals, fungi, and bacteria-derived compounds have been proved to be efficient and safe for treating human herpesvirus infection. This review covers the natural antiherpetic agents with the chemical structural class of alkaloids, flavonoids, terpenoids, polyphenols, anthraquinones, anthracyclines, and miscellaneous compounds, and their antiviral mechanisms have been summarized. This review would be helpful to get a better grasp of anti-herpesvirus activity of natural products and their derivatives, and to evaluate the feasibility of natural compounds as an alternative therapy against herpesvirus infections in humans.     

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

The genus Datura (Solanaceae) contains nine species of medicinal plants that have held both curative utility and cultural significance throughout history. This genus’ particular bioactivity results from the enormous diversity of alkaloids it contains, making it a valuable study organism for many disciplines. Although Datura contains mostly tropane alkaloids (such as hyoscyamine and scopolamine), indole, beta-carboline, and pyrrolidine alkaloids have also been identified. The tools available to explore specialized metabolism in plants have undergone remarkable advances over the past couple of decades and provide renewed opportunities for discoveries of new compounds and the genetic basis for their biosynthesis. This review provides a comprehensive overview of studies on the alkaloids of Datura that focuses on three questions: How do we find and identify alkaloids? Where do alkaloids come from? What factors affect their presence and abundance? We also address pitfalls and relevant questions applicable to natural products and metabolomics researchers. With both careful perspectives and new advances in instrumentation, the pace of alkaloid discovery—from not just Datura—has the potential to accelerate dramatically in the near future.     

Strategies for the Synthesis of Functional Naphthalene Diimides

Naphthalene diimides, which have for a long time been in the shadow of their higher homologues the perylene diimides, currently belong to the most investigated classes of organic compounds. This is primarily due to the initial synthetic studies on core functionalization that were carried out at the beginning of the last decade, which facilitated diverse structural modifications of the naphthalene scaffold. Compounds with greatly modified optical and electronic properties that can be easily and effectively modulated by appropriate functionalization were made accessible through relatively little synthetic effort. This resulted in diverse interesting applications. The electron‐deficient character of these compounds makes them highly valuable, particularly in the field of organic electronics as air‐stable n‐type semiconductors, while absorption bands over the whole visible spectral range through the introduction of core substituents enabled interesting photosystems and photovoltaic applications. This Review provides an overview on different approaches towards core functionalization as well as on synthetic strategies for the core expansion of naphthalene diimides that have been developed mainly in the last five years.     

Secondary metabolites for antiulcer activity

Peptic ulcers are open sores or erosions in the lining of either the duodenum (duodenal ulcers) or the stomach (gastric ulcers). Peptic ulcer, which is mainly caused by bacterial attack or excess of acid secretion, can be cured effectively by these isolated plant compounds. In this present scenario, demand for herbal medicines are increasing due to easy availability in surrounding place at low cost. This review article is all about such isolated plant compounds such as alkaloids, flavonoids and terpenoids. Various plants have been used as folk medicine by the people of rural area, which shows significant effect against peptic ulcer. Further study should be conducted upon these herbal plants because there is possibility for minimising the adverse effect caused by the present antiulcer drugs.     

Detection and identification of loline and its analogues in horse urine

Several kinds of loline-type alkaloids, norloline, loline, N-acetylnorloline, N-acetylloline, N-formylnorloline, N-formylloline and N-methylloline were detected in the urine of race-horses. Furthermore, a new compound of the alkaloids, N-senecioylnorloline, was also found and identified. These compounds were mainly identified by means of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-fourier transform-infrared spectrometry (GC-FT-IR). A certain plant of Gramineae containing four kinds of loline-type alkaloids was found in a bale of hay used for the horse forage. The taxonomic feature of the plant was different from known plants containing loline-type alkaloids. The common fragmentation of loline-type alkaloids under electron ionization was briefly discussed.     

Analysis of steroidal glycoalkaloids and their metabolites in Solanum nigrum fruits based on liquid chromatography-tandem mass spectrometry and molecular networking

Solanum nigrum fruit is like a treasure house for anticancer drugs because of its steroidal alkaloids. However, the clinical treatment of cancer mainly uses immature fruits, which can cause a toxic reaction if eaten directly, while mature fruits are eaten as fruit. In order to clarify the reasons for the differences in pharmacodynamics and toxicity between them, we studied the composition and metabolism of steroidal alkaloids in fruits of different maturities based on liquid chromatography-tandem mass spectrometry and molecular networking. As a result, 114 steroidal glycoalkaloids were identified. During fruit ripening, the aglycones of steroidal alkaloids mainly undergo hydroxylation and carboxylation, and the sugar side chains mainly undergo acylation and glycosylation reactions. Furthermore, 219 steroidal alkaloids were identified in a metabolism experiment in rats. Metabolic processes include deglycosylation, redox, sulfuric acid binding, acetyl binding, and glucuronic acid-binding. Steroidal alkaloids in mature fruits have high molecular weight and polarity, which are difficult to absorb, and most of them are excreted through feces and urine, which may be the reason for their poor efficacy. This study lays a foundation for research on the biosynthesis of steroidal alkaloids and provides potential candidates for the discovery of new steroidal alkaloid anticancer drugs.     

Aconitum lipo-alkaloids--semisynthetic products of the traditional medicine

The term lipo-alkaloid is used for C19 aconitane alkaloids containing one or two long-chain fatty acid residues. Lipo-alkaloids are transesterified derivatives of the most toxic and highly effective diester-type diterpene alkaloids, such as aconitine, hypaconitine, mesaconitine. Lipo-alkaloids are native minor compounds of aconite drugs, but their amount significantly increases after traditional processing, which is a general method in the Far Eastern traditional medicinal systems. Analytical works demonstrated that cautious processing (usually boiling) of crude aconite roots decreases the amount of normal diterpene alkaloids and increases the concentration of lipo-alkaloids resulting in the reduction of toxicity of the drugs. Many papers reported that lipo-alkaloids occur as a complex mixture in the drugs, and the isolation of the individual components is extremely difficult. These compounds have been identified using highly sensitive analytical methods (HPLC-MS, NMR), and semisynthetic approaches have been developed to ensure lipo-alkaloids in pure form for pharmacological studies. This review summarizes the structure, chemistry, semisynthesis, analytics and bioactivities of lipo-alkaloids. On the basis of 32 references this is the first comprehensive study on this topic, covering the data of 173 compounds.     

Applications of in vivo and in vitro solid-phase microextraction techniques in plant analysis: A review

As a very popular sample preparation technique, solid-phase microextraction (SPME) coupled with various analytical instrumentation, has been widely used for the determination of trace levels of different plant compounds, such as volatile organic compounds (VOCs) emitted from the different plant organs, and environmental contaminants in plants. In this review, recent applications of in vitro and in vivo SPME in plant analysis are discussed and summarized according to the different organs of plants, including fruits, flowers, leaves, stems, roots and seeds, and the whole plant as well. Future developments and applications of SPME in plant analysis, especially in vivo sampling approaches, are also prospected.     

Biosynthesis of metal and metal oxide nanoparticles using various parts of plants for antibacterial,antifungal and anticancer activity: A review

The synthesis of several metal oxide nanoparticles mediated by microbes and plants and their different bio-applications gain more attention from the research community in the biomedical science field. As concerned with plants, which comprise plenty of biofunctional compounds like alkaloids, steroids, tannins, nutritionals, and flavonoids. As reported plant-mediated biogenic fabrication of the metal oxide nanoparticles at an eco-friendly, less hazardous, and low cost is a convincing way, further, it is treated for biological screening in terms of applications like antifungal, cytotoxicity, antibacterial, and anti-plasmodia activity. These dose-dependent activities and the morphology (shape, size) also impact the efficiency of the bio-inspired NPs. The eco-friendly way of using plant material highlights their non-hazardous nature, cost-ineffective, and facile which is an alternative to synthesizing chemically. Plants rich in metabolites or chemicals may act as reducing and capping agents during the synthesis of NPs. The present review reveals a plant-mediated synthesis of metal and metal oxide NPs, their morphological analysis like shape and size, crystalline nature using several techniques, and their biological applications.     

Indanoyl amino acid conjugates: tunable elicitors of plant secondary metabolism

The unassuming nature of plants belies their viciously effective defensive strategies in the face of herbivore attack. Under the direction of, among others, octadecanoid hormones, plants respond by producing phytoalexins, bitter and toxic alkaloids, protease inhibitors, and even volatile compounds that call predatory insects to the herbivores. A rational design of 4-oxoindanoyl amino acid conjugates based on the phytotoxin, coronatine, as a structural guide resulted in a series of highly active compounds which turn on defensive systems in much the same way as octadecanoid hormones. The developments in the syntheses of indanoyl amino acid conjugates have created easy access to substantial amounts of a variety of such compounds. When these compounds were tested in biological systems, they showed abilities to induce defensive responses that surpassed octadecanoid hormones. In addition, small changes in the structures of these compounds resulted in large differences in the particular defensive systems that were activated. Indanoyl amino acid conjugates are promising tools in photoaffinity approaches towards the macromolecular targets of octadecanoids and their subcellular localization. Owing to the strong activation of plant defense or their efficient induction of fruit abscission which facilitates mechanical harvest, the compounds are promising candidates for future application in agriculture.     

Diversity in Chemical Structures and Biological Properties of Plant Alkaloids

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.     

Amaryllidaceae,sceletium, imidazole,oxazole, thiazole,peptide and miscellaneous alkaloids

This review covers alkaloids classified in the plant families Amaryallidaceae and Sceletium. In addition alkaloids possessing imidazole, oxazole and thiazole structures are listed followed by alkaloids possessing peptide linkages. Finally miscellaneous alkaloids include those compounds found naturally which cannot be classified into known groups; a relative Pandora's box. A total of 620 structures has been reviewed from 218 references found in the literature for the period July 1999 to June 2000.     

Classification,Toxicity and Bioactivity of Natural Diterpenoid Alkaloids

Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing ‘compounds’ structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognised bioactivity.     

Collision cross section measurement and prediction methods in omics

Omics studies such as metabolomics, lipidomics, and proteomics have become important for understanding the mechanisms in living organisms. However, the compounds detected are structurally different and contain isomers, with each structure or isomer leading to a different result in terms of the role they play in the cell or tissue in the organism. Therefore, it is important to detect, characterize, and elucidate the structures of these compounds. Liquid chromatography and mass spectrometry have been utilized for decades in the structure elucidation of key compounds. While prediction models of parameters (such as retention time and fragmentation pattern) have also been developed for these separation techniques, they have some limitations. Moreover, ion mobility has become one of the most promising techniques to give a fingerprint to these compounds by determining their collision cross section (CCS) values, which reflect their shape and size. Obtaining accurate CCS enables its use as a filter for potential analyte structures. These CCS values can be measured experimentally using calibrant-independent and calibrant-dependent approaches. Identification of compounds based on experimental CCS values in untargeted analysis typically requires CCS references from standards, which are currently limited and, if available, would require a large amount of time for experimental measurements. Therefore, researchers use theoretical tools to predict CCS values for untargeted and targeted analysis. In this review, an overview of the different methods for the experimental and theoretical estimation of CCS values is given where theoretical prediction tools include computational and machine modeling type approaches. Moreover, the limitations of the current experimental and theoretical approaches and their potential mitigation methods were discussed.