Chemoinformatics methods for systematic comparison of molecules from natural and synthetic sources and design of hybrid libraries

Until recently, the field of diversity and library design has more or less ignored natural products as a compound source. This is probably due to at least two reasons. First, combinatorial and reaction-based approaches have been major focal points in the early days of computational library design. In addition, a widespread view is that natural products are often highly complex and not amenable to medicinal chemistry efforts. This contribution introduces recent computational approaches to systematically analyze natural molecules and bridge the gap between natural products and synthetic chemistry programs. Large scale comparisons of natural and synthetic molecules are discussed as well as studies designed to identify `synthetic mimics' of natural products with specific activity. In addition, a concept for the design of natural/synthetic hybrid libraries is introduced. Although research in this area is still in its early stages, an important lesson to be learned from computational analyses is that there is no need to a priori `shy away' from natural products as a source for molecular design.     

A study of chemical composition and radiation attenuation properties in clinoptilolite-rich natural zeolite from Turkey

Clinoptilolite, a type of natural zeolite, has been commonly used as pozzolanic additive in concrete. This type of natural zeolite is generally used as a mineral admixture by substitution in Portland cement to produce high performance concretes. In the present study, the major, minor and trace element levels present in the clinoptilolite-rich natural zeolite (CRNZ) have been determined using a wavelength dispersive X-ray fluorescence spectrometer. Also, the clinoptilolite-rich natural zeolite has been compared with Portland cement with respect to the radiation attenuation properties. From the results it can be concluded that due to the natural radioactive content of clinoptilolite-rich natural zeolite (CRNZ) even if it is in trace level and also due to the poorer X-ray attenuation compared with Portland cement, special care should be taken to use this type of natural zeolite as blend materials in cements, etc.     

Characterization of natural rubber concerning its components and molecular weight in Taraxacum kok-saghyz Rodin using pyrolysis gas chromatography-mass spectrometry

Taraxacum kok-saghyz Rodin (TKS) has abundant natural rubber in its root and the molecular weight of its natural rubber is higher than that in Hevea brasiliensis. Thus, TKS is an excellent alternative for the commercial production of natural rubber. The content and molecular weight of natural rubber are two qualitative indicators. Efficient determination for both indicators is still a challenge. In this study, we developed a method to simultaneously determine the content and molecular weight of natural rubber in TKS with pyrolysis－gas chromatography-mass spectrometry. The content of natural rubber was quantified by internal standard method. We optimized the pyrolysis temperature and chromatographic method during content determination. The limits of detection and quantification were 0.47 and 1.56 μg, respectively. In addition, the arachidonic acid methyl ester, an unsaturated fatty acid proposed from the α-end group of natural rubber, was quantified to obtain the number of natural rubber polymers. Based on the content and the polymer number, we also quantified the molecular weight of natural rubber. Thus, the content and molecular weight of natural rubber were simultaneously determined in TKS. Our study provides a new perspective for the high throughput analysis of natural rubber.     

具有生理活性的天然有机化合物

本文从天然药物、天然农药、生长及生态调节物质、精神依赖药物和全合成等几个方面, 通过评论一些有较大社会意义或学术价值的化合物, 试图透视具有生理活性天然有机化合物这一常盛不衰的热点研究领域的发展脉络, 及对人类生活的意义。     

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.     

Chemomics and drug innovation

Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules (natural product building blocks) through a sequence of enzyme catalytic reactions.For each reaction,the natural product building blocks may contribute a group of atoms to the target natural product.We describe this group of atoms as a chemoyl.A chemome is the complete set of chemoyls in an organism.Chemomics studies chemomes and the principles of natural product syntheses and evolutions.Driven by survival and reproductive demands,biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes;this results in biological and chemical diversity.In recent years,it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening.Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems,and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening.This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.     

化学基元组学与药物创新

化学基元组学（chemomics）是与化学信息学、生物信息学、合成化学等学科相关的交叉学科．生物系统从内源性小分子（天然砌块）出发,通过酶催化的化学反应序列制造天然产物．生物系统通过化学反应和天然砌块向目标天然产物“砌入”一组原子,这样的一组原子称为化学基元（chemoyl）．化学基元组（chemome）是生物组织中所含有的化学基元的全体．化学基元组学研究各种化学基元的结构、组装与演化的基本规律．在生存压力和繁衍需求的驱动下,生物系统已经进化出有效手段来合成天然产物以应付环境的变化,并产生了丰富多彩的生物和化学多样性．近年来,人们意识到药物创新的瓶颈之一是药物筛选资源的日益枯竭．化学基元组学可以解决这个瓶颈问题,它通过揭示生物系统制备化学多样性的规律,发展仿生合成方法制备类天然化合物库（quasi natural product libraries）以供药物筛选．本文综述了化学基元组学的主要研究内容及其在药物创新各领域中的潜在应用．     

Effect of non‐rubber components on the mechanical properties of natural rubber

Effect of the nanomatrix structure on mechanical properties of natural rubber was investigated in relation to the strain‐induced crystallization. Structure of natural rubber was analyzed through Fourier transform infrared spectroscopy, wide‐angle X‐ray diffraction measurement and transmission electron microscopy. The nanomatrix of the non‐rubber components was found to be inevitably formed in natural rubber, in which natural rubber particles linking to fatty acids were dispersed in the nanomatrix of the proteins and phospholipids. The nanomatrix disappeared after deproteinization of natural rubber with urea. Tensile strength and modulus of natural rubber were reduced by removal of the fatty acids and the proteins, which resulted in disappearance of the nanomatrix structure. The effect of fatty acids on the crystallization of natural rubber in small particles as a dispersoid was proved by tensile test of blend of natural rubber and styrene butadiene rubber. Copyright © 2016 John Wiley & Sons, Ltd.     

Size-expanded DNA bases: an ab initio study of their structural and electronic properties

The size-expanded DNA bases, xA, xC, xG, and xT, are benzo-homologue forms of the natural DNA bases; i.e., their structure can be seen as the fusion of a natural base and a benzene ring. Recently, a variety of DNAs, known as xDNAs, have been synthesized in which size-expanded and natural bases are paired. In this paper we use second-order M?ller-Plesset perturbation theory and density functional theory to investigate the structural and electronic properties of xA, xC, xG, and xT and their natural counterparts. We find that whereas natural and size-expanded bases have both nonplanar amino groups the latter have also nonplanar aromatic rings. When density functional theory is used to investigate the electronic properties of size-expanded and natural bases, it is found that the HOMO-LUMO gap of the size-expanded bases is smaller than that of the natural bases. Also, xG should be easier to oxidize than G.     

Applications of total synthesis toward the discovery of clinically useful anticancer agents

This tutorial review provides a historical sampling of synthetic efforts undertaken in our laboratory, which have led to the total syntheses of a range of small molecule natural products of potential interest in oncology. It has become evident that natural products, and structures clearly derivable from natural products, have a remarkable record in the treatment of cancer at the clinical level. It is likely that, with the growing power of chemical synthesis, small molecule natural products will play a continuing role in providing lead anticancer compounds.     

合成天然气水合物实验研究

天然气水合物(NGH)是天然气与水在低温高压条件下形成的笼形物,亦称可燃冰.在冻土带和海洋中已发现大量天然气水合物,是清洁燃料的后续天然资源,但开采技术尚不成熟.由于1m~3天然气水合物在常温下可释放约164m~3的天然气和0.8m~3的水,因此合成天然气水合物,可实现天然气的固态运输,更便于在天然气汽车上的储存.本文介绍天然气水合物的基本性质及其人工合成研究取得的进展.     

Future Prospective of Radiopharmaceuticals from Natural Compounds Using Iodine Radioisotopes as Theranostic Agents

Natural compounds provide precursors with various pharmacological activities and play an important role in discovering new chemical entities, including radiopharmaceuticals. In the development of new radiopharmaceuticals, iodine radioisotopes are widely used and interact with complex compounds including natural products. However, the development of radiopharmaceuticals from natural compounds with iodine radioisotopes has not been widely explored. This review summarizes the development of radiopharmaceuticals from natural compounds using iodine radioisotopes in the last 10 years, as well as discusses the challenges and strategies to improve future discovery of radiopharmaceuticals from natural resources. Literature research was conducted via PubMed, from which 32 research articles related to the development of natural compounds labeled with iodine radioisotopes were reported. From the literature, the challenges in developing radiopharmaceuticals from natural compounds were the purity and biodistribution. Despite the challenges, the development of radiopharmaceuticals from natural compounds is a golden opportunity for nuclear medicine advancement.     

Web search and data mining of natural products and their bioactivities in PubChem

Natural products,as major resources for drug discovery historically,are gaining more attentions recently due to the advancement in genomic sequencing and other technologies,which makes them attractive and amenable to drug candidate screening.Collecting and mining the bioactivity information of natural products are extremely important for accelerating drug development process by reducing cost.Lately,a number of publicly accessible databases have been established to facilitate the access to the chemical biology data for small molecules including natural products.Thus,it is imperative for scientists in related fields to exploit these resources in order to expedite their researches on natural products as drug leads/candidates for disease treatment.PubChem,as a public database,contains large amounts of natural products associated with bioactivity data.In this review,we introduce the information system provided at PubChem,and systematically describe the applications for a set of PubChem web services for rapid data retrieval,analysis,and downloading of natural products.We hope this work can serve as a starting point for the researchers to perform data mining on natural products using PubChem.     

高通量天然产物化学和毛细管核磁共振探头技术的应用

介绍了近几年为高通量药物筛选构建大型天然产物样品库的高通量天然产物化学,即多通道平行高效液相制备和平行液质联用分析技术;详细介绍了核磁共振新技术即体积小和质量灵敏度高的毛细管核磁共振探头技术,该探头技术的成功应用使得天然产物样品库中活性化合物的结构鉴定所需样品量降低到前所未有的微克级水平;展望了源于中药的天然产物作为小分子探针开展脑功能方面的化学基因组学研究。     

A New Model for the Genesis of Natural Gases--Multi-source Overlap, Multi-stage Continuity, Type Controlled by Main Source and Nomenclature by Main Stage (Ⅰ)--Multi-source Overlap and Type Controlled by Main Source

Based on the geochemical studies of natural gases in the past ten years in China, the authors have proposed a new model for their genesis--multi-source overlap, multi-stage continuity, main source-controlling type and nomenclature by the main stage.Multi-source refers to a diversity of material sources involved in the formation of natural gases, including abiogenic and biogenic material sources. In regard to biogenic sources, either oil-generating or coal-generating organic matter would produce gaseous hydrocarbon reservoirs of commercial importance. Generally, natural gases originating from these sources can overlap to form gas reservoirs. Under specific circumstances mantle-source abiogenic gases could overlap biogenic gases to form gas reservoirs. In nature, natural gases predominated by gaseous hydrocarbons may be formed from a single end-member source. However, multi-source overlap is more typical of the genesis of natural gases.     

Short Overview of Some Assays for the Measurement of Antioxidant Activity of Natural Products and Their Relevance in Dermatology

Impaired systemic redox homeostasis is implicated in the onset and development of various diseases, including skin diseases. Therefore, continuous search for natural products with antioxidant bioactivities applicable in biomedicine is attractive topic of general interest. Research efforts aiming to validate antioxidant potentials of natural products has led to the development of several assays based on various test principles. Hence, understanding the advantages and limitations of various assays is important for selection of assays useful to study antioxidant and related bioactivities of natural products of biomedical interest. This review paper gives a short overview on some chemical and cellular bioassays used to estimate the antioxidant activity of chosen natural products together with a brief overview on the use of natural products with antioxidant activities as adjuvant medicinal remedies in dermatology.     

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.     

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.     

康德伦理学中的道德法则与自然法则

康德伦理学以区别两类法则即自然法则和道德法则为前提。但在康德对于道德法则或道德义务的论证过程中,呈现出一种复杂的情形：一方面,就人的生命本体的欲求（体现着自然生命内在的合目的性）而言,康德认为人的理性应当超越它而追求不以自己的幸福为目的的道德自由,或把履行道德义务看成是高于对自己幸福追求的职事。另一方面,康德则采用合于人的自然生命本体的自然法则,来论证或证成道德法则。在康德证成道德义务的四个著名个案中,有三个个案都是以自然法则来进行辩护的。这些“自然法则”对于人的有机生命本体的关注面虽然不一样,但都是从这样一个自然本体出发。因此,为康德所拒绝的又被康德召唤回来。康德伦理学对待人的自然生命本体及其法则的两面态度,是其伦理学中一个十分值得关注的理论问题。     

Biomimetic synthesis of pyrone-derived natural products: exploring chemical pathways from a unique polyketide precursor

Our biomimetic hypothesis proposes that families of diverse natural products with complex core structures such as 9,10-deoxytridachione, photodeoxytridachione and ocellapyrone A are derived in nature from a linear and conformationally strained all-( E) tetraene-pyrone precursor. We therefore synthesized such a precursor and investigated its biomimetic transformation under a variety of reaction conditions, both to the above natural products as well as to diverse isomers which we propose to be natural products "yet to be discovered". We also report herein the first synthesis of the natural product iso-9,10-deoxytridachione.