Natural Products and Semi-Synthetic Compounds as Antithrombotics: A Review of the Last Ten Years (2009-2019)

2020 ◽  
pp. 65-107
Author(s):  
Angelo Piato ◽  
Cedric Stephan Graebin
Keyword(s):  
Natural Products ◽  
Synthetic Compounds

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joelle Ngo Hanna ◽  
Boris D. Bekono ◽  
Luc C. O. Owono ◽  
Flavien A. A. Toze ◽  
James A. Mbah ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Functional Groups ◽  
Atomic Composition ◽  
Synthetic Compounds ◽  
Chemical Libraries ◽  
Synthetic Drugs ◽  
Drugs Analysis ◽  
Chemical Class

Abstract In the quest to know why natural products (NPs) have often been considered as privileged scaffolds for drug discovery purposes, many investigations into the differences between NPs and synthetic compounds have been carried out. Several attempts to answer this question have led to the investigation of the atomic composition, scaffolds and functional groups (FGs) of NPs, in comparison with synthetic drugs analysis. This chapter briefly describes an atomic enumeration method for chemical libraries that has been applied for the analysis of NP libraries, followed by a description of the main differences between NPs of marine and terrestrial origin in terms of their general physicochemical properties, most common scaffolds and “drug-likeness” properties. The last parts of the work describe an analysis of scaffolds and FGs common in NP libraries, focusing on huge NP databases, e.g. those in the Dictionary of Natural Products (DNP), NPs from cyanobacteria and the largest chemical class of NP – terpenoids.

scholarly journals Fragment Library of Natural Products and Compound Databases for Drug Discovery

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1518 ◽  
Author(s):  
Ana L. Chávez-Hernández ◽  
Norberto Sánchez-Cruz ◽  
José L. Medina-Franco
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Synthetic Compounds ◽  
Drug Candidates ◽  
Compound Libraries ◽  
Chemical Database ◽  
Fragment Library ◽  
Further Development ◽  
Fragment Libraries ◽  
Fragment Based Drug Discovery

Natural products and semi-synthetic compounds continue to be a significant source of drug candidates for a broad range of diseases, including coronavirus disease 2019 (COVID-19), which is causing the current pandemic. Besides being attractive sources of bioactive compounds for further development or optimization, natural products are excellent substrates of unique substructures for fragment-based drug discovery. To this end, fragment libraries should be incorporated into automated drug design pipelines. However, public fragment libraries based on extensive collections of natural products are still limited. Herein, we report the generation and analysis of a fragment library of natural products derived from a database with more than 400,000 compounds. We also report fragment libraries of a large food chemical database and other compound datasets of interest in drug discovery, including compound libraries relevant for COVID-19 drug discovery. The fragment libraries were characterized in terms of content and diversity.

Natural products and synthetic compounds as immunomodulators

2003 ◽  
Vol 1 (2) ◽  
pp. 319-335 ◽  
Author(s):  
Oliver Kayser ◽  
K Noël Masihi ◽  
Albrecht F Kiderlen
Keyword(s):  
Natural Products ◽  
Synthetic Compounds

scholarly journals Expanding the Fluorine Chemistry of Living Systems Using Engineered Polyketide Synthase Pathways

Science ◽  
2013 ◽  
Vol 341 (6150) ◽  
pp. 1089-1094 ◽  
Author(s):  
Mark C. Walker ◽  
Benjamin W. Thuronyi ◽  
Louise K. Charkoudian ◽  
Brian Lowry ◽  
Chaitan Khosla ◽  
...  
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Natural Product ◽  
Polyketide Synthase ◽  
Building Blocks ◽  
Living Systems ◽  
Synthetic Compounds ◽  
Fluorinated Building Blocks

Organofluorines represent a rapidly expanding proportion of molecules that are used in pharmaceuticals, diagnostics, agrochemicals, and materials. Despite the prevalence of fluorine in synthetic compounds, the known biological scope is limited to a single pathway that produces fluoroacetate. Here, we demonstrate that this pathway can be exploited as a source of fluorinated building blocks for introduction of fluorine into natural-product scaffolds. Specifically, we have constructed pathways involving two polyketide synthase systems, and we show that fluoroacetate can be used to incorporate fluorine into the polyketide backbone in vitro. We further show that fluorine can be inserted site-selectively and introduced into polyketide products in vivo. These results highlight the prospects for the production of complex fluorinated natural products using synthetic biology.

Natural Products: Key Prototypes to Drug Discovery Against Neglected Diseases Caused by Trypanosomatids

2020 ◽  
Vol 27 (13) ◽  
pp. 2133-2146 ◽  
Author(s):  
Marina Themoteo Varela ◽  
João Paulo S. Fernandes
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Neglected Tropical Diseases ◽  
Biological Activities ◽  
Neglected Diseases ◽  
Synthetic Compounds ◽  
Structural Variety ◽  
The World ◽  
Leishmania Spp ◽  
Per Se

Background: Neglected tropical diseases are a group of infections caused by microorganisms and viruses that affect mainly poor regions of the world. In addition, most available drugs are associated with long periods of treatment and high toxicity which limits the application and patient compliance. Investment in research and development is not seen as an attractive deal by the pharmaceutical industry since the final product must ideally be cheap, not returning the amount invested. Natural products have always been an important source for bioactive compounds and are advantageous over synthetic compounds when considering the unique structural variety and biological activities. On the other hand, isolation difficulties and low yields, environmental impact and high cost usually limit their application as drug per se. Objective: In this review, the use of natural products as prototypes for the semi-synthesis or total synthesis, as well as natural products as promising hits is covered, specifically regarding compounds with activities against trypanosomatids such as Trypanosoma spp. and Leishmania spp. Methods: Selected reports from literature with this approach were retrieved. Conclusion: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites.

ChemInform Abstract: Statistical Investigation into the Structural Complementarity of Natural Products and Synthetic Compounds.

ChemInform ◽  
2010 ◽  
Vol 30 (24) ◽  
pp. no-no
Author(s):  
Thomas Henkel ◽  
Roger M. Brunne ◽  
Hartwig Mueller ◽  
Felix Reichel
Keyword(s):  
Natural Products ◽  
Statistical Investigation ◽  
Synthetic Compounds

Rhodium(III)-Catalyzed C–H Activation-Based First Total Synthesis of 6-O-Methyl Anciscochine, an Alkaloid Isolated from Ancistrocladus tectorius

Synthesis ◽  
2019 ◽  
Vol 52 (01) ◽  
pp. 119-126
Author(s):  
Didier F. Vargas ◽  
Brenda S. Romero ◽  
Enrique L. Larghi ◽  
Teodoro S. Kaufman
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Methyl Acrylate ◽  
One Pot ◽  
Synthetic Compounds ◽  
Mediated Reduction

The concise and efficient first total synthesis of 6-O-methyl anciscochine, employing a tandem C–C/C–N formation approach via a rhodium-catalyzed C–H activation/alkenylation/annulation strategy, is reported. This heterocycle was isolated from the liana Ancystrocladus tectorius and features a unique 3-hydroxymethylisoquinoline core that is found in a few other natural products and in some bioactive synthetic compounds. The synthesis, which was executed in four high-yielding steps and a global yield of 43%, involved the oximation of commercial 2,4-dimethoxyacetophenone under CeCl3·7H2O-promotion, followed by pivaloylation of the oxime. A one-pot pivaloxime-directed alkenyl­ation/annulation stage with methyl acrylate, furthered by a NaBH4/ CaCl2­-mediated reduction of the resulting isoquinoline 3-carboxylate ester completed the sequence.

The aggregation response of Trichostrongylus colubriformis: a basis for the rapid interpretation of in vitro anthelmintic screens

Parasitology ◽  
1986 ◽  
Vol 93 (3) ◽  
pp. 531-537 ◽  
Author(s):  
D. C. Jenkins ◽  
E. B. Rapson ◽  
P. Topley
Keyword(s):  
Natural Products ◽  
Mass Screening ◽  
Broad Spectrum ◽  
Culture Medium ◽  
Intrinsic Activity ◽  
Trichostrongylus Colubriformis ◽  
Synthetic Compounds ◽  
Aggregation Response ◽  
Blood Sucking

SUMMARYAn in vitro anthelmintic primary screen in which the effects of compounds on the aggregation response of newly moulted adult worms of Trichostrongylus colubriformis was monitored is described. Representatives of all the major classes of the anti-trichostrongyle anthelmintics all inhibited worm aggregation completely when present in the culture medium either at or at less than micromolar concentrations. The screen proved highly selective for these broad-spectrum agents, much higher concentrations of the narrower spectrum anthelmintics, active only against blood-sucking nematodes, trematodes and/or cestodes, having little or no effect on this response. This in vitro assay, based solely on the occurrence or absence of worm aggregation following the final moult in culture, proved very easy to interpret rapidly and accurately. It can be recommended therefore for the primary mass screening of synthetic compounds or natural products for intrinsic activity against the trichostrongylid helminths of ruminants.

scholarly journals Radioprotective natural products as alternative complements in oncological radiotherapy

2021 ◽  
Vol 20 (2) ◽  
pp. 101-122
Author(s):  
Subhajit Dutta ◽  
◽  
Raju R Wadekar ◽  
Tilottama Roy ◽  
◽  
...  
Keyword(s):  
Natural Products ◽  
Radiation Therapy ◽  
Medical Treatment ◽  
High Energy ◽  
Integrative Oncology ◽  
Synthetic Compounds ◽  
Conventional Medical Treatment ◽  
Major Shift ◽  
Ionising Radiations ◽  
Cancerous Cells

Humans when exposed to harmful ionising radiations suffer from various pathophysiological disorders including cancer. Radiotherapy is a treatment where these cancerous cells within a tumor are targeted and killed by means of high energy waves. This therapy is very expensive and involves highly sophisticated instruments. In addition to this, most synthetic radioprotectors including Amifostine have been found to possess toxicity. This led researchers to develop a novel, economically viable, and efficient therapeutic alternative to radiation therapy. The last two decades have observed a major shift towards investigating natural products as radioprotectors, as these are immensely effective in terms of their potential bioequivalence relative to many of the established synthetic compounds available. Taking into account the limitations of radiation therapy, an approach ‘Integrative Oncology’ that involves a combination of both traditional and conventional medical treatment are used nowadays to treat patients suffering from cancer and associated mental and psychological disorders.

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