The most widely used specialized chemistry databases and web services allowing access to them will be described. Besides the largest commercial three (Reaxys, SciFinder, Web of Science), some freely available services (Google Scholar, ChemSpider , PubChem, PubMed) will also be discussed. Strong and weak points of the presented databases will be emphasised and recommendations for optimal database selection and searching will be given.
INTRODUCTION: Pyrazine is a member of 1,4-diazines, which constitute an important class of heterocycles. Various pyrazine derivatives have been synthesized and successfully evaluated as agents with diverse pharmacological effects (including but not limited to antiproliferative, anti-infective, and effects on cardiovascular or nervous system) and some of them have become clinically used drugs worldwide. AREA COVERED: This review is a survey of important patents on pyrazine derivatives with pharmacological activity published in the period June 2012 - July 2014. The patent databases SciFinder and esp@cenet were used to locate patent applications. EXPERT OPINION: Pyrazine derivatives possess numerous noteworthy pharmacological effects, including antimycobacterial, antibacterial, antifungal, antidiabetic, diuretic, anticancer, antiviral, hypnotic, and analgesic. The class of pyrazine-based candidate drugs has experienced a rapid growth both in absolute numbers of investigated compounds and in the spectrum of diverse biological activities. We expect that several of these compounds will add to existing pharmaceuticals in the very near future. According to the number of compounds and filed patents, the most promising areas are: i) inhibitors of protein kinases (applicable as antiproliferatives); and ii) inhibitors of β-secretase (applicable for the treatment of Alzheimer's disease).
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- Alzheimer Disease drug therapy enzymology MeSH
- Drug Industry legislation & jurisprudence MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- Humans MeSH
- Molecular Structure MeSH
- Neuroprotective Agents pharmacology MeSH
- Patents as Topic * MeSH
- Cell Proliferation drug effects MeSH
- Pyrazines chemistry pharmacology therapeutic use MeSH
- Drug Design MeSH
- Amyloid Precursor Protein Secretases antagonists & inhibitors metabolism MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
INTRODUCTION: Enoyl-(acyl-carrier-protein) reductase (ENR) is a limiting step enzyme in the Fatty Acid Synthase II system. In mammals, there is no homologue to ENR, which makes it an optimal candidate target for selective anti-infective drugs. Up-to-date, only two ENR inhibitors are used in clinical practice. AREA COVERED: This review is a survey on important patents on low molecular weight compounds with ENR inhibiting activity published in 2011-2015. Common patent databases (SciFinder, esp@cenet, WIPO) were used to locate patent applications on the proposed topic and in the timespan of 2011-2015. EXPERT OPINION: In 2011-2015, we have observed patents in previously known structural groups of diphenyl ethers and acrylamides as well as new structural classes, often identified by high-throughput screening campaigns. The spectrum of activity of applied derivatives covers significant bacteria, mycobacteria, and apicomplexan parasites (Plasmodia and Toxoplasma). Good news from research of ENR inhibitors: a) four selective anti-staphylococcal compounds applied in 2011-2015 or earlier were pushed to Phase I or Phase II clinical trials and some of them proved safety and tolerability after peroral and/or intravenous administration; b) big pharma companies have renewed their interest in the development of new anti-infective compounds against resistant strains of clinical relevance.
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- Drug Resistance, Microbial MeSH
- Anti-Infective Agents adverse effects pharmacology therapeutic use MeSH
- Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) antagonists & inhibitors metabolism MeSH
- Enzyme Inhibitors adverse effects pharmacology therapeutic use MeSH
- Humans MeSH
- Patents as Topic MeSH
- Drug Design MeSH
- High-Throughput Screening Assays MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Natural phenolics are secondary plant metabolites, which can be divided into several categories with the common structural feature of phenolic hydroxyl. The biological activity of phenolics is often modified and enhanced by prenylation by prenyl and geranyl; higher terpenoid chains are rare. The type of prenyl connection and modification affects their biological activity. OBJECTIVE: This review summarizes information about prenylated phenols and some of their potential sources, and provides an overview of their anti-inflammatory potential in vitro and in vivo. METHOD: The literature search was performed using SciFinder and keywords prenyl, phenol, and inflammation. For individual compounds, an additional search was performed to find information about further activities and mechanisms of effects. RESULT: We summarized the effects of prenylated phenolics in vitro in cellular or biochemical systems on the production and release of inflammation-related cytokines; their effects on inhibition of cyclooxygenases and lipoxygenases; the effects on production of nitric oxide, antiradical and antioxidant activity; and the effect on the inhibition of the release of enzymes and mediators from neutrophils, mast cells and macrophages. The information about the antiphlogistic potential of prenylated phenolics is further supported by a review of their action in animal models. CONCLUSION: Almost 400 prenylated phenols were reviewed to overview their antiinflammatory effect. The bioactivity of several prenylated phenols was confirmed also using in vivo assays. A pool of natural prenylated phenols represents a source of inspiration for synthesis, and prenylated phenols as components of various medicinal plants used to combat inflammation could be their active principles.
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- Anti-Inflammatory Agents chemistry pharmacology MeSH
- Phenols chemistry pharmacology MeSH
- Plants, Medicinal MeSH
- Humans MeSH
- Molecular Structure MeSH
- Prenylation MeSH
- Plant Extracts chemistry MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Cyclosporine A (CsA) is widely used for organ transplantation and autoimmune disorders. However, CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA. The metabolism of CsA has a close relationship with this disease in renal-transplant patients. However, the metabolic pathways of CsA and its metabolizing enzymes have rarely been comprehensively reviewed. In this review, we have summarized the specific metabolic profiles of CsA in humans, especially renal-transplant patients. Moreover, the specific metabolizing enzymes and the potential roles that CsA metabolism plays in CsA nephrotoxicity were summarized and discussed. METHODS: Electronic databases including PubMed, Web of Science, and Scifinder were searched with the keywords "Cyclosporine A and metabolism", and "Cyclosporine A and nephrotoxicity", "Cyclosporine A metabolism and nephrotoxicity". All these studies published until 2018 were included in this review. RESULTS: The major metabolic pathways of CsA in humans are hydroxylation and N-demethylation. Normally, these metabolites are relatively less toxic than CsA. However, the metabolism of CsA in the kidneys is much weaker than that in the liver, which explains why CsA is so toxic to the kidneys. CYP3A families, especially CYP3A4 and CYP3A5, play an important role in the biotransformation of CsA. Moreover, increased lines of evidence show that some metabolites (including AM19) associate directly with nephrotoxicity in CsA-treated organ-transplant patients. CONCLUSION: The findings of this review help to further understand the metabolic activities of CsA in renal-transplant patients and cast some light on the mechanisms of CsA nephrotoxicity.
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- Cyclosporine adverse effects pharmacokinetics MeSH
- Glucose metabolism MeSH
- Immunosuppressive Agents adverse effects pharmacokinetics MeSH
- Humans MeSH
- Metabolic Networks and Pathways MeSH
- Kidney Diseases chemically induced metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Piperazine, a six membered nitrogen containing heterocycle, is of great significance to the rational design of drugs. This moiety can be found in a plethora of well-known drugs with various therapeutic uses, such as antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardio protectors, anti-inflammatory, and imaging agents. Slight modification to the substitution pattern on the piperazine nucleus facilitates a recognizable difference in the medicinal potential of the resultant molecules. AREAS COVERED: Scifinder was the main source used to search for patents containing piperazine compounds with therapeutic uses. The article describes a variety of molecular designs bearing piperazine entity furnishing CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, antidiabetic, and antihistamine profiles, as well as agents relieving pain and useful in imaging applications. EXPERT OPINION: The great interest gathered to explore piperazine based molecules in relatively few years reflects the broad potential of the entity. Earlier, this scaffold was considered to express CNS activity only. However, a significant increase in research covering studies of several different activities of piperazine ring suggest a successful emergence of the pharmacophore. Certain patents outlined in the present article recommend that piperazines can be a flexible building block to discover drug-like elements and modification of substituents present on the piperazine ring may have a significant impact on the pharmacokinetic and pharmacodynamics factors of the resulting molecules. This article aims to provide insights to piperazine based molecular fragments that would assist drug discoverers to rationally design molecules for various diseases. We anticipate, and highly recommend, further therapeutic investigations on this motif.
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- Humans MeSH
- Drug Discovery methods MeSH
- Patents as Topic MeSH
- Piperazines chemistry pharmacology therapeutic use MeSH
- Drug Design * MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha gossypiifolia L. (Euphorbiaceae) is popularly known as bellyache bush or black physic nut and is widely used in local / traditional medicine due to the various biological activities attributed to its different parts, including its leaves, roots, and latex. AIM OF THE STUDY: In this review, we aim to update and discuss the chemistry, specific pharmacology, and toxicological activities of Jatropha gossypiifolia and its bioactive metabolites. MATERIALS AND METHODS: The Web of Science, PubMed, Google Scholar, SciFinder, Cochrane Library, Scopus, and Science Direct databases were searched with the name "Jatropha gossypiifolia" and the term "bioactive metabolites". All studies on the chemistry, pharmacology, and toxicology of the plant up to December 2018 were included in this review. RESULTS: Jatropha gossypiifolia leaves are considered to have anti-inflammatory, antimicrobial and insecticidal properties. The root and stem have anti-inflammatory and antimicrobial properties. The seeds and fruits can be used against influenza and as a sedative, analgesic or anti-diarrheal agents. The latex is bactericidal and molluscicidal. Topical application of latex is used to treat wounds and bites of venomous animals. The diluted form is usually used for the treatment of diarrhoea by indigenous peoples. CONCLUSIONS: The main pharmacological activities of Jatropha gossypiifolia include anti-inflammatory, antineoplastic, antimicrobial, antioxidant, and anticholinesterase, and antihypertensive activities. Species of Jatropha are notably known for their toxic potential, and their toxicity is primarily related to the latex and seed contents. However, the potential mechanisms of these pharmacological activities have not been fully explored. We hope this review will help to further inform the potential utilization of Jatropha gossypiifolia in complementary and alternative medicine.
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- Ethnopharmacology MeSH
- Jatropha chemistry metabolism MeSH
- Humans MeSH
- Plant Leaves MeSH
- Plant Extracts adverse effects metabolism pharmacology MeSH
- Medicine, Traditional adverse effects methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Various pieces of evidence have shown that people who consume foods rich in polyphenolic and flavonoids compounds have a lower incidence of inflammatory, autoimmune diseases and cancer. OBJECTIVE: The study aimed to review the most potent compounds that affect the immune response and diseases associated with it. METHODS: Publications in PubMed and EmBase, from 1974-2018, and patents form Free patents online, Scifinder, Espacenet and Mendeley in which flavonoids, their semi-synthetic and synthetic derivatives are involved in immunosuppressive or immunostimulatory responses in vitro and in vivo. RESULTS: In vitro, flavonoids and their derivatives inhibit various transcriptional factors, which modulate differentiation, proliferation, activation of immune cells and enhance regulatory T cell generation. Some flavonoids exert anti-inflammatory effects through: Blockade of NF-κB, and NLRP3 inflammasome, inhibition of pro-inflammatory cytokine production, IL-1β, IL-2, IL-6, TNF-α, IL-17A, down regulation of chemokines, and reduction of reactive oxygen and nitrogen species. Nevertheless, several reports have shown that some flavonoids enhance immune response by enhancing: oxygen and nitrogen radicals, antibody production, cytotoxic activity against tumours by increasing activating receptors and down regulating inhibitory receptors. In consequence, flavonoids may be potentially useful for treatment of infectious diseases and cancer. CONCLUSION: The most potent flavonoids in inflammation that modify immune responses are apigenin, quercetin and Epigallocatechin-3-Gallate (EGCG) although, other compounds are still under study and cannot be excluded. The most relevant patents concerning the use of flavones and other polyphenols were revised. A promising future of these compounds in different therapies is discussed.
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- Anti-Inflammatory Agents therapeutic use MeSH
- Autoimmune Diseases immunology therapy MeSH
- Immunity, Cellular MeSH
- Cytokines metabolism MeSH
- Flavonoids therapeutic use MeSH
- Humans MeSH
- Inflammation Mediators metabolism MeSH
- Neoplasms immunology therapy MeSH
- NF-kappa B metabolism MeSH
- Patents as Topic MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
INTRODUCTION: Nuclear magnetic resonance (NMR) measurement of 1 JCC coupling by two-dimensional (2D) INADEQUATE (incredible natural abundance double quantum transfer experiment), which is a special case of double-quantum (DQ) spectroscopy that offers unambiguous determination of 13 C-13 C spin-spin connectivities through the DQ transitions of the spin system, is especially suited to solving structures rich in quaternary carbons and poor in hydrogen content (Crews rule). OBJECTIVE: To review published literature on the application of NMR methods to determine structure in the liquid-state, which specifically considers the interaction of a pair of carbon-13 (13 C) nuclei adjacent to one another, to allow direct tracing out of contiguous carbon connectivity using 2D INADEQUATE. METHODOLOGY: A comprehensive literature search was implemented with various databases: Web of Knowledge, PubMed and SciFinder, and other relevant published materials including published monographs. The keywords used, in various combinations, with INADEQUATE being present in all combinations, in the search were 2D NMR, 1 JCC coupling, natural product, structure elucidation, 13 C-13 C connectivity, cryoprobe and CASE (computer-assisted structure elucidation)/PANACEA (protons and nitrogen and carbon et alia). RESULTS: The 2D INADEQUATE continues to solve "intractable" problems in natural product chemistry, and using milligram quantities with cryoprobe techniques combined with CASE/PANACEA experiments can increase machine time efficiency. The 13 C-13 C-based structural elucidation by dissolution single-scan dynamic nuclear polarisation NMR can overcome disadvantages of 13 C insensitivity at natural abundance. Selected examples have demonstrated the trajectory of INADEQUATE spectroscopy from structural determination to clarification of metabolomics analysis and use of DFT (density functional theory) and coupling constants to clarify the connectivity, hybridisation and stereochemistry within natural products. CONCLUSIONS: Somewhat neglected over the years because of perceived lack of sensitivity, the 2D INADEQUATE NMR technique has re-emerged as a useful tool for solving natural products structures, which are rich in quaternary carbons and poor in hydrogen content.
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- Biological Products * MeSH
- Carbon Isotopes MeSH
- Skeleton MeSH
- Magnetic Resonance Spectroscopy MeSH
- Metabolomics MeSH
- Carbon * MeSH
- Publication type
- Journal Article MeSH
