Statistical Investigation into the Structural Complementarity of Natural Products and Synthetic Compounds

The potential of new natural products as an important source for the exploration and development of new drugs and crop protection products is a long way from being exhausted. The statistical analysis of the structures of the natural and synthetically derived compounds has shown conspicuous variations in structural types in the natural products derived from different natural sources, which can be utilized in the search for individual active substances. The occasionally voiced prepossession that natural products have already been sufficiently examined and therefore no more innovations are to be expected can definitely be rejected.     

芳香类化合物异戊烯基化的研究进展

结构多样的芳香类化合物一直被用作新药发现的线索或主要来源。通过对类药物天然产物进行异戊烯基化结构修饰,能有效提高芳香类化合物生物活性及生物利用度,为新药研究与开发提供简便高效的方法。本文综述了近年来芳香类化合物异戊烯基化的各种方法,以为今后研究提供参考。     

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection,Neurological Disorders,and Neuroblastoma

Monoamine oxidase inhibitors (MAOIs) are an important class of drugs prescribed for treatment of depression and other neurological disorders. Evidence has suggested that patients with atypical depression preferentially respond to natural product MAOIs. This review presents a comprehensive survey of the natural products, predominantly from plant sources, as potential new MAOI drug leads. The psychoactive properties of several traditionally used plants and herbal formulations were attributed to their MAOI constituents. MAO inhibitory constituents may also be responsible for neuroprotective effects of natural products. Different classes of MAOIs were identified from the natural product sources with non-selective as well as selective inhibition of MAO-A and -B. Selective reversible natural product MAOIs may be safer alternatives to the conventional MAOI drugs. Characterization of MAO inhibitory constituents of natural products traditionally used as psychoactive preparations or for treatment of neurological disorders may help in understanding the mechanism of action, optimization of these preparations for desired bioactive properties, and improvement of the therapeutic potential. Potential therapeutic application of natural product MAOIs for treatment of neuroblastoma is also discussed.     

Dereplication and targeted isolation of bioactive sulphur compound from bacteria isolated from a hydrothermal field

Marine micro-organisms in the deep-sea hydrothermal vent systems are considered as potential sources of bioactive natural products. Sixteen bacterial strains were isolated from a deep-sea hydrothermal field and screened for bioactive metabolism studies. After the strains were subjected to bioactive testing at different culture media, chemical dereplication by HPLC coupled to high-resolution mass spectrometer was performed to analyse or determine the main secondary metabolisms in those strains. Strain 06204 was large-scale fermented with relative optimal media, for isolating the desired sulphur compound. Butyrolactone I 3-sulphate was isolated and structurally identified from the extract, guided by dereplication and showed moderate antivirus activities against H3N2 and EV71 viruses. Our study suggests that deep-sea hydrothermal bacteria are good sources of sulphur natural products. Meanwhile, the described approach, mainly bioactive screening, dereplication and targeted isolation, is effective and efficient to discover interesting bioactive compounds in hydrothermal bacteria.     

Natural Products Targeting the Mitochondria in Cancers

There are abundant sources of anticancer drugs in nature that have a broad prospect in anticancer drug discovery. Natural compounds, with biological activities extracted from plants and marine and microbial metabolites, have significant antitumor effects, but their mechanisms are various. In addition to providing energy to cells, mitochondria are involved in processes, such as cell differentiation, cell signaling, and cell apoptosis, and they have the ability to regulate cell growth and cell cycle. Summing up recent data on how natural products regulate mitochondria is valuable for the development of anticancer drugs. This review focuses on natural products that have shown antitumor effects via regulating mitochondria. The search was done in PubMed, Web of Science, and Google Scholar databases, over a 5-year period, between 2015 and 2020, with a keyword search that focused on natural products, natural compounds, phytomedicine, Chinese medicine, antitumor, and mitochondria. Many natural products have been studied to have antitumor effects on different cells and can be further processed into useful drugs to treat cancer. In the process of searching for valuable new drugs, natural products such as terpenoids, flavonoids, saponins, alkaloids, coumarins, and quinones cover the broad space.     

Property distributions: differences between drugs,natural products,and molecules from combinatorial chemistry

The differences between three different compound classes, natural products, molecules from combinatorial synthesis, and drug molecules, were investigated. The major structural differences between natural and combinatorial compounds originate mainly from properties introduced to make combinatorial synthesis more efficient. These include the number of chiral centers, the prevalence of aromatic rings, the introduction of complex ring systems, and the degree of the saturation of the molecule as well as the number and ratios of different heteroatoms. As drug molecules derive from both natural and synthetic sources, they cover a joint area in property space of natural and combinatorial compounds. A PCA-based scheme is presented that differentiates the three classes of compounds. It is suggested that by mimicking certain distribution properties of natural compounds, combinatorial products might be made that are substantially more diverse and have greater biological relevance.     

Prevention of Enzymatic Browning by Natural Extracts and Genome-Editing: A Review on Recent Progress

Fresh fruits and vegetable products are easily perishable during postharvest handling due to enzymatic browning reactions. This phenomenon has contributed to a significant loss of food quality and appearance. Thus, a safe and effective alternative method from natural sources is needed to tackle enzymatic browning prevention. The capabilities of natural anti-browning agents derived from plant- and animal-based resources in inhibiting enzymatic activity have been demonstrated in the literature. Some also possess strong antioxidants properties. This review aims to summarize a recent investigation regarding the use of natural anti-browning extracts from different sources for controlling the browning. The potential applications of genome-editing in preventing browning activity and improving postharvest quality is also discussed. Moreover, the patents on the anti-browning extract from natural sources is also presented in this review. The information reviewed here could provide new insights, contributing to the development of natural anti-browning extracts and genome-editing techniques for the prevention of food browning.     

Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.     

The role of bioactive compounds on the promotion of neurite outgrowth

Neurite loss is one of the cardinal features of neuronal injury. Apart from neuroprotection, reorganization of the lost neuronal network in the injured brain is necessary for the restoration of normal physiological functions. Neuritogenic activity of endogenous molecules in the brain such as nerve growth factor is well documented and supported by scientific studies which show innumerable compounds having neurite outgrowth activity from natural sources. Since the damaged brain lacks the reconstructive capacity, more efforts in research are focused on the identification of compounds that promote the reformation of neuronal networks. An abundancy of natural resources along with the corresponding activity profiles have shown promising results in the field of neuroscience. Recently, importance has also been placed on understanding neurite formation by natural products in relation to neuronal injury. Arrays of natural herbal products having plentiful active constituents have been found to enhance neurite outgrowth. They act synergistically with neurotrophic factors to promote neuritogenesis in the diseased brain. Therefore use of natural products for neuroregeneration provides new insights in drug development for treating neuronal injury. In this study, various compounds from natural sources with potential neurite outgrowth activity are reviewed in experimental models.     

Thermal decomposition of pyrite

Thermal decomposition of natural pyrite (cubic, FeS₂) has been investigated using X-ray diffraction and⁵⁷Fe Mössbauer spectroscopy. X-ray diffraction analysis of pyrite ore from different sources showed the presence of associated minerals, such as quartz, szomolnokite, stilbite or stellerite, micas and hematite. Hematite, maghemite and pyrrhotite were detected as thermal decomposition products of natural pyrite. The phase composition of the thermal decomposition products depends on the temperature, time of heating and starting size of pyrite crystals. Hematite is the end product of the thermal decomposition of natural pyrite.     

Natural products and Pharma 2011: strategic changes spur new opportunities

Although natural products have been marginalized by major pharmaceutical companies over the last 20-30 years, the changing landscape of drug discovery now favors a greatly enhanced role for Nature's privileged structures. Screening for drug leads in phenotypic screens provides the best opportunity to realize the value of natural products. Advances in total synthesis, especially function-oriented syntheses and biosynthetic technologies offer new avenues for the medicinal chemical optimization of biologically active secondary metabolites. Genomic research has given new insights into biosynthetic processes as well as providing evidence that a wealth of unrealized biosynthetic potential remains to be explored. As Pharma strives to develop innovative and highly effective new drugs, natural products will be increasingly valued as sources of novel leads whose further development will be expedited by emerging technologies.     

用组合化学建立天然产物类似物库

天然产物是药物先导化合物的重要来源.组合化学技术在天然产物的研究中起着越来越重要的作用.目前已构建并合成了许多以天然产物为模板的化合物库,为基于天然产物的药物研究开辟了广阔的空间.     

Natural Product Synthesis at the Interface of Chemistry and Biology

Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences.     

Actin-binding marine macrolides: total synthesis and biological importance

Marine organisms produce a fascinating range of structurally diverse secondary metabolites, which often possess unusual and sometimes unexpected biological activities. This structural diversity makes these marine natural products excellent molecular probes for the investigation of biochemical pathways. Recently, a number of novel and stereochemically complex macrolides, having a large macrolactone (22- to 44-membered) ring, that interact with the actin cycloskeleton have been isolated from different marine sources. Actin, like tubulin, is a major component of the cytoskeleton and has important cellular functions. Although the details of these interactions are still under investigation, these marine macrolides are becoming increasingly important as novel molecular probes to help elucidate the cellular functions of actin. Owing to their potent antitumor activities, these compounds, for example the aplyronines, also have potential for preclinical development in cancer chemotherapy. Their appealing molecular structures, with an abundance of stereochemistry, and biological significance, coupled with the extremely limited availability from the marine sources, have stimulated enormous interest in the synthesis of these compounds. This review summarizes the biological properties of these unusual marine natural products and features the recently completed total syntheses of swinholide A, scytophycin C, aplyronine A, mycalolide A--all of these being potent cytotoxic agents that target actin--and a diastereoisomer of ulapualide A. Rather than detailing each individual step of these multistep total syntheses, the different synthetic strategies, key reactions, and methods adopted for controlling the stereochemistry are compared.     

八种黄酮类天然产物对高危型HPV16/18 E6蛋白的分子对接研究

宫颈癌以其高发病率和高死亡率严重危害女性健康,传统治疗手段有效率低且治疗过程给患者带来极大痛苦。近年来,许多天然植物来源化合物已被确定为治疗和预防宫颈癌的有希望的药物来源,但天然产物治疗癌症的具体作用机制尚未明确。因此,本文选取了8种黄酮类天然小分子抑制剂,分别与高危型HPV16/18 E6蛋白重要位点LxxLL疏水口袋进行分子对接研究,以期探索天然产物抗宫颈癌的作用机制。对接分析显示,这些天然产物均与HPV18E6蛋白LxxLL疏水口袋产生较强相互作用,与HPV16 E6蛋白对接时,木犀草素则比其他7种黄酮类化合物结合得更为深入,这些相互作用可能有助于p53功能的恢复。对接分析有助于理解蛋白质-配体相互作用的分子机制,为设计治疗HPV感染的新药提供依据。     

Phytochemical profiles,antioxidant and anti-acetylcholinesterasic activities of the leaf extracts of Rhamnus lycioides subsp. oleoides (L.) Jahand. & Maire in different solvents

In this work, the extracts obtained with different solvents from the leaves of Rhamnus lycioides subsp. oleoides (L.) Jahand. & Maire were studied for their phytochemical profile and then for their antioxidant and acetylcholinesterase inhibitory activities. The phytochemical profiles of the extracts in n-hexane, dichloromethane, ethyl acetate, methanol, anthraquinone rich and water, showed the presence of different compounds belonging to several classes of natural products such as flavonoids, anthraquinones, saccharides and fatty acids. For what concerns the biological tests, the ethyl acetate, methanol and anthraquinone rich extracts showed the highest activities in both assays due to the high amount of compounds possessing those properties such as flavonoids and anthraquinones. By consequence, these specific extracts of the species may be considered to be potential sources of natural antioxidant and anti-acetylcholinesterasic compounds.     

Plant Natural Products: Promising Resources for Cancer Chemoprevention

Cancer is a major factor threatening human health and life safety, and there is a lack of safe and effective therapeutic drugs. Intervention and prevention in premalignant process are effective ways to reverse carcinogenesis and prevent cancer from occurring. Plant natural products are rich in sources and are a promising source for cancer chemoprevention. This article reviews the chemopreventive effects of natural products, especially focused on polyphenols, flavonoids, monoterpene and triterpenoids, sulfur compounds, and cellulose. Meanwhile, the main mechanisms include induction of apoptosis, antiproliferation and inhibition of metastasis are briefly summarized. In conclusion, this article provides evidence for natural products remaining a prominent source of cancer chemoprevention.     

Recent advances in C–S bond construction to synthesize sulfone

Sulfone is prevalent in natural products and has been widely used in organic chemistry. Among the approaches of installing sulfonyl group, sulfonylation starting from stable and environmentally friendly sulfonyl sources is promising and attractive. Diverse mild sulfonyl sources such as DABSO, inorganic metal salts, sulfinic acids/salts, and sulfonyl hydrazides have been applied to construct sulfone. In this review, recent advances for the sulfonylation under transition metal catalysis and metal-free conditions are summarized.     

Marine cytotoxic macrolides haterumalides and biselides, and related natural products

Marine animals and plants are rich sources of bioactive natural products. Haterumalides and biselides, isolated from Okinawan marine animals, are 14-membered macrolides with strong cytotoxicity against human cancer cell lines. This review highlights the isolation, structures, bioactivities, and total synthesis of haterumalides, biselides, and related natural products.     

Characterization of a Bio-sourced,Fluorescent, Ratiometric pH Indicator with Alkaline pKa

Utilizing organisms as sources of fluorophores relieves the demand for petroleum feedstock in organic synthesis of fluorescent products, and endophytic fungi provide a promising vein for natural fluorescent products. We report the characterization of a pH-responsive fluorophore from an endophytic fungus isolated from sand pine. The endogenous fluorescence of the live organism was measured using fluorescence microscopy. Computational interpretation of the spectra was accomplished with time-dependent density functional theory methods. The combined use of experimental and theoretically predicted spectra revealed the pH equilibria and photoexcited tautomerization of the natural product, 5-methylmellein. This product shows promise both as a stand-alone pH-indicating fluorophore, with alkaline pK_a, and as "green" feedstock for synthesis of custom fluorophores.