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Theranostics 2021Triptolide, an abietane-type diterpenoid isolated from Hook. F., has significant pharmacological activity. Research results show that triptolide has obvious inhibitory... (Review)
Review
Triptolide, an abietane-type diterpenoid isolated from Hook. F., has significant pharmacological activity. Research results show that triptolide has obvious inhibitory effects on many solid tumors. Therefore, triptolide has become one of the lead compounds candidates for being the next "blockbuster" drug, and multiple triptolide derivatives have entered clinical research. An increasing number of researchers have developed triptolide synthesis methods to meet the clinical need. To provide new ideas for researchers in different disciplines and connect different disciplines with researchers aiming to solve scientific problems more efficiently, this article reviews the research progress made with analyzes of triptolide pharmacological activity, biosynthetic pathways, and chemical synthesis pathways and reported in toxicological and clinical studies of derivatives over the past 20 years, which have laid the foundation for subsequent researchers to study triptolide in many ways.
Topics: Antineoplastic Agents, Phytogenic; Diterpenes; Epoxy Compounds; Humans; Phenanthrenes; Tripterygium
PubMed: 34158845
DOI: 10.7150/thno.57745 -
International Journal of Molecular... Apr 2023Epoxide hydrolases are attractive and industrially important biocatalysts. They can catalyze the enantioselective hydrolysis of epoxides to the corresponding diols as... (Review)
Review
Epoxide hydrolases are attractive and industrially important biocatalysts. They can catalyze the enantioselective hydrolysis of epoxides to the corresponding diols as chiral building blocks for bioactive compounds and drugs. In this review article, we discuss the state of the art and development potential of epoxide hydrolases as biocatalysts based on the most recent approaches and techniques. The review covers new approaches to discover epoxide hydrolases using genome mining and enzyme metagenomics, as well as improving enzyme activity, enantioselectivity, enantioconvergence, and thermostability by directed evolution and a rational design. Further improvements in operational and storage stabilization, reusability, pH stabilization, and thermal stabilization by immobilization techniques are discussed in this study. New possibilities for expanding the synthetic capabilities of epoxide hydrolases by their involvement in non-natural enzyme cascade reactions are described.
Topics: Epoxide Hydrolases; Catalysis; Epoxy Compounds; Hydrolysis; Genetic Techniques; Stereoisomerism
PubMed: 37108499
DOI: 10.3390/ijms24087334 -
Biomedicine & Pharmacotherapy =... Jun 2023Celastrol, triptolide and triptonide are the most significant active ingredients of Tripterygium wilfordii Hook F (TWHF). In 2007, the 'Cell' journal ranked celastrol,... (Review)
Review
A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes.
Celastrol, triptolide and triptonide are the most significant active ingredients of Tripterygium wilfordii Hook F (TWHF). In 2007, the 'Cell' journal ranked celastrol, triptolide, artemisinin, capsaicin and curcumin as the five natural drugs that can be developed into modern medicinal compounds. In this review, we collected relevant data from the Web of Science, PubMed and China Knowledge Resource Integrated databases. Some information was also acquired from government reports and conference papers. Celastrol, triptolide and triptonide have potent pharmacological activity and evident anti-cancer, anti-tumor, anti-obesity and anti-diabetes effects. Because these compounds have demonstrated unique therapeutic potential for acute and chronic inflammation, brain injury, vascular diseases, immune diseases, renal system diseases, bone diseases and cardiac diseases, they can be used as effective drugs in clinical practice in the future. However, celastrol, triptolide and triptonide have certain toxic effects on the liver, kidney, cholangiocyte heart, ear and reproductive system. These shortcomings limit their clinical application. Suitable combination therapy, new dosage forms and new routes of administration can effectively reduce toxicity and increase the effect. In recent years, the development of different targeted drug delivery formulations and administration routes of celastrol and triptolide to overcome their toxic effects and maximise their efficacy has become a major focus of research. However, in-depth investigation is required to elucidate the mechanisms of action of celastrol, triptolide and triptonide, and more clinical trials are required to assess the safety and clinical value of these compounds.
Topics: Humans; Triterpenes; Diterpenes; Phenanthrenes; Epoxy Compounds; Neoplasms
PubMed: 37062220
DOI: 10.1016/j.biopha.2023.114705 -
IARC Monographs on the Evaluation of... 2000
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Cricetinae; Disease Models, Animal; Environmental Exposure; Epoxy Compounds; Female; Humans; Male; Maximum Allowable Concentration; Mice; Neoplasms, Experimental; Propanols; Rats
PubMed: 11100412
DOI: No ID Found -
International Journal of Molecular... Mar 2023Polypropionate units are a common structural feature of many of the natural products in polyketides, some of which have shown a broad range of antimicrobial and... (Review)
Review
Polypropionate units are a common structural feature of many of the natural products in polyketides, some of which have shown a broad range of antimicrobial and therapeutic potential. Polypropionates are composed of a carbon skeleton with alternating methyl and hydroxy groups with a specific configuration. Different approaches have been developed for the synthesis of polypropionates and herein we include, for the first time, all of the epoxide-based methodologies that have been reported over the years by several research groups such as Kishi, Katsuki, Marashall, Miyashita, Prieto, Sarabia, Jung, McDonald, etc. Several syntheses of polypropionate fragments and natural products that employed epoxides as key intermediates have been described and summarized in this review. These synthetic approaches involve enatio- and diastereoselective synthesis of epoxides (epoxy-alcohols, epoxy-amides, and epoxy-esters) and their regioselective cleavage with carbon and/or hydride nucleophiles. In addition, we included a description of the isolation and biological activities of the polypropionates and related natural products that have been synthetized using epoxide-based approaches. In conclusion, the epoxide-based methodologies are a non-aldol alternative approach for the construction of polypropionate.
Topics: Epoxy Compounds; Biological Products; Stereoisomerism; Carbon; Alcohols
PubMed: 37047173
DOI: 10.3390/ijms24076195 -
Molecules (Basel, Switzerland) Mar 2021Cyclic imides belong to a well-known class of organic compounds with various biological activities, promoting a great interest in compounds with this functional group....
Cyclic imides belong to a well-known class of organic compounds with various biological activities, promoting a great interest in compounds with this functional group. Due to the structural complexity of some molecules and their spectra, it is necessary to use several spectrometric methods associated with auxiliary tools, such as the theoretical calculation for the structural elucidation of complex structures. In this work, the synthesis of epoxy derivatives of 5-methylhexahydroisoindole-1,3-diones was carried out in five steps. Diels-Alder reaction of isoprene and maleic anhydride followed by reaction with -anisidine afforded the amide (). Esterification of amide () with methanol in the presence of sulfuric acid provided the ester () that cyclized in situ to give imides and . Epoxidation of and with -chloroperbenzoic acid (MCPBA) afforded and . The diastereomers were separated by silica gel flash column chromatography, and their structures were determined by analyses of the spectrometric methods. Their structures were confirmed by matching the calculated H and C NMR chemical shifts of ( and ) with the experimental data of the diastereomers using MAE, CP3, and DP4 statistical analyses. Biological assays were carried out to evaluate the potential herbicide activity of the imides. Compounds and inhibited root growth of the weed by more than 70% at all the concentrations evaluated.
Topics: Bidens; Cucumis sativus; Epoxy Compounds; Herbicides; Imides; Lactuca; Molecular Structure; Seeds; Sorghum
PubMed: 33808049
DOI: 10.3390/molecules26071923 -
British Journal of Industrial Medicine Nov 1980The purpose of this review is to consider whether epoxides represent a hazard to human health. Possible means of occupational and non-occupational exposure are discussed... (Review)
Review
The purpose of this review is to consider whether epoxides represent a hazard to human health. Possible means of occupational and non-occupational exposure are discussed with reference to the production and uses of industrially important compounds and other epoxides, such as naturally occurring plant and fungal products. In addition to epoxides themselves, unsaturated compounds that may be metabolised in vivo to epoxides are included, since this appears to be a further important means of exposure. The toxicology, in particular carcinogenicity and mutagenicity, is discussed, along with a brief outline of the biochemistry such as metabolism, binding to cell constituents, and DNA repair mechanisms. The question of interactions between different epoxides in vivo is also raised.
Topics: Animals; Drug Interactions; Environmental Exposure; Epoxy Compounds; Ethers, Cyclic; Humans; Mice; Mutagens; Neoplasms, Experimental; Nucleic Acids; Occupational Diseases; Proteins; Rats; Structure-Activity Relationship
PubMed: 7004476
DOI: 10.1136/oem.37.4.317 -
IARC Monographs on the Evaluation of... 1999
Topics: Aldehydes; Animals; Carcinogenicity Tests; Carcinogens; Epoxy Compounds; Humans; Mutagenicity Tests; Mutagens; Skin Neoplasms
PubMed: 10476428
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1989
Topics: Animals; Carcinogens; Chemical Phenomena; Chemistry; Epoxy Compounds; Ethers, Cyclic; Humans; Risk Factors
PubMed: 2636274
DOI: No ID Found -
Basic & Clinical Pharmacology &... Sep 2017Human beings are exposed to many reactive electrophiles, both formed endogenously and from exogenous exposures. Such compounds could react with cellular biomolecules and... (Review)
Review
Human beings are exposed to many reactive electrophiles, both formed endogenously and from exogenous exposures. Such compounds could react with cellular biomolecules and form stable reaction products, adducts, at nucleophilic sites in proteins and DNA, constituting a risk for toxic effects. Adductomic approaches aim to study the totality of adducts, to specific biomolecules, by mass spectrometric screening. This Mini-Review focuses on the development and application of an adductomic approach for the screening of unknown adducts to N-terminal valine (Val) in haemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC-MS/MS). The approach is based on the FIRE procedure, a modified Edman procedure for the analysis of adducts to N-terminal Val in Hb by LC-MS/MS. In the first application of the approach, samples from 12 smokers/non-smokers were screened for Hb adducts, and six previously identified adducts and 20 unknown adducts were detected. To confirm the observation of the detected unknown adducts, targeted screenings were performed in larger sets of blood samples (n = 50-120) from human cohorts. The majority of the previously detected unknown adducts was found in all analysed samples, with large interindividual variations in adduct levels. For structural identification of unknown adducts, a strategy using adductome LC-MS/MS data was formulated and applied. Six identified adducts correspond to ethylation and the precursor electrophiles ethyl vinyl ketone, glyoxal, methylglyoxal, acrylic acid and 1-octen-3-one. The observation of these adducts in human blood motivate further studies to evaluate possible contributions to health risks, as well as their potential as biomarkers of exposure.
Topics: Aldehydes; Biomarkers; Chromatography, Liquid; DNA Adducts; Environmental Exposure; Epoxy Compounds; Hemoglobins; Humans; Nitrosamines; Tandem Mass Spectrometry; Valine
PubMed: 27889941
DOI: 10.1111/bcpt.12715