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Molecules (Basel, Switzerland) Nov 2021Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries... (Review)
Review
Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC, and biological targets of inhibition are therefore presented in this review.
Topics: Antineoplastic Agents; Biological Products; Epidermal Growth Factor; Fibroblast Growth Factors; Heterocyclic Compounds; Humans; Neoplasms; Platelet-Derived Growth Factor; Receptors, Neuropeptide Y; Thymidine Phosphorylase; Vascular Endothelial Growth Factor A
PubMed: 34885716
DOI: 10.3390/molecules26237134 -
Chembiochem : a European Journal of... Jun 2020Five new members of the salinilactone family, salinilactones D-H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or...
Five new members of the salinilactone family, salinilactones D-H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or shortened alkyl side chains relative to the recently reported salinilactones A-C. They were identified by GC/MS, gas chromatographic retention index, and comparison with synthetic samples. We further investigated the occurrence of salinilactones across six newly proposed Salinispora species to gain insight into how compound production varies among taxa. The growth-inhibiting effect of this compound family on multiple biological systems including non-Salinispora actinomycetes was analyzed. Additionally, we found strong evidence for significant cytotoxicity of the title compounds.
Topics: Actinobacteria; Actinoplanes; Aquatic Organisms; Biological Products; Gas Chromatography-Mass Spectrometry; Lactones; Microbial Sensitivity Tests; Micromonospora; Micromonosporaceae; Molecular Structure
PubMed: 31957947
DOI: 10.1002/cbic.201900764 -
Natural Product Reports Jan 2021Covering: 2010-2020The digital revolution is driving significant changes in how people store, distribute, and use information. With the advent of new technologies around... (Review)
Review
Covering: 2010-2020The digital revolution is driving significant changes in how people store, distribute, and use information. With the advent of new technologies around linked data, machine learning and large-scale network inference, the natural products research field is beginning to embrace real-time sharing and large-scale analysis of digitized experimental data. Databases play a key role in this, as they allow systematic annotation and storage of data for both basic and advanced applications. The quality of the content, structure, and accessibility of these databases all contribute to their usefulness for the scientific community in practice. This review covers the development of databases relevant for microbial natural product discovery during the past decade (2010-2020), including repositories of chemical structures/properties, metabolomics, and genomic data (biosynthetic gene clusters). It provides an overview of the most important databases and their functionalities, highlights some early meta-analyses using such databases, and discusses basic principles to enable widespread interoperability between databases. Furthermore, it points out conceptual and practical challenges in the curation and usage of natural products databases. Finally, the review closes with a discussion of key action points required for the field moving forward, not only for database developers but for any scientist active in the field.
Topics: Anti-Bacterial Agents; Biological Products; Biosynthetic Pathways; Databases, Chemical; Databases, Factual; Databases, Pharmaceutical; Information Storage and Retrieval; Metabolomics; Microbiology; Multigene Family
PubMed: 32856641
DOI: 10.1039/d0np00053a -
Marine Drugs Feb 2022Natural products from plants have been listed for hundreds of years as a source of biologically active molecules. In recent years, the marine environment has... (Review)
Review
Natural products from plants have been listed for hundreds of years as a source of biologically active molecules. In recent years, the marine environment has demonstrated its ability to provide new structural entities. More than 70% of our planet's surface is covered by oceans, and with the technical advances in diving and remotely operated vehicles, it is becoming easier to collect samples. Although the risk of rediscovery is significant, the discovery of silent gene clusters and innovative analytical techniques has renewed interest in natural product research. Different strategies have been proposed to activate these silent genes, including co-culture, or mixed fermentation, a cultivation-based approach. This review highlights the potential of co-culture of marine microorganisms to induce the production of new metabolites as well as to increase the yields of respective target metabolites with pharmacological potential, and moreover to indirectly improve the biological activity of a crude extract.
Topics: Animals; Aquatic Organisms; Biological Products; Coculture Techniques; Complex Mixtures; Fermentation; Humans; Multigene Family
PubMed: 35200682
DOI: 10.3390/md20020153 -
Genes May 2023Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic...
Psoriasis is a systemic inflammatory disease that associates with multiple comorbidities. It involves complex interactions between environmental factors and polygenic predisposition. The IL-17 family is one of the main actors in the pathogenesis of psoriasis. Secondary nonresponse is common, especially during the long-term use of TNF-α inhibitors, but it is not uncommon even for newer biologics, such as IL-17 inhibitors. Identification of clinically useful biomarkers of treatment efficacy and safety would enable optimal treatment selection, improve patient quality of life and outcome, and reduce healthcare costs. To our knowledge, this is the first study to evaluate the relationship between genetic polymorphism of IL-17F (rs763780) and IL-17RA (rs4819554) and response to biological treatment and other clinical data in bio-naive and secondary non-responders psoriasis patients in Romania and Southeastern Europe. We performed a prospective, longitudinal, analytical cohort study of 81 patients diagnosed with moderate-to-severe chronic plaque psoriasis who received biological treatments for the first time. Of the 79 patients treated with TNF-α inhibitors, 44 experienced secondary nonresponse. All patients were genotyped for the two SNPs in IL-17F and IL-17RA genes. The rs763780 polymorphism in the IL-17F gene could be an attractive candidate biomarker for predicting which patients will respond to anti-TNF-α therapies. Another emergent association of rs4819554 in IL-17RA with the risk of nail psoriasis and a higher BMI in moderate-to-severe plaque psoriasis patients is described.
Topics: Humans; Biological Products; Cohort Studies; Interleukin-17; Polymorphism, Single Nucleotide; Prospective Studies; Psoriasis; Quality of Life; Tumor Necrosis Factor Inhibitors; Receptors, Interleukin-17
PubMed: 37239484
DOI: 10.3390/genes14051123 -
Marine Drugs Aug 2021Worldwide, 19.3 million new cancer cases and almost 10.0 million cancer deaths occur each year. Recently, much attention has been paid to the ocean, the largest... (Review)
Review
Worldwide, 19.3 million new cancer cases and almost 10.0 million cancer deaths occur each year. Recently, much attention has been paid to the ocean, the largest biosphere of the earth that harbors a great many different organisms and natural products, to identify novel drugs and drug candidates to fight against malignant neoplasms. The marine compounds show potent anticancer activity in vitro and in vivo, and relatively few drugs have been approved by the U.S. Food and Drug Administration for the treatment of metastatic malignant lymphoma, breast cancer, or Hodgkin's disease. This review provides a summary of the anticancer effects and mechanisms of action of selected marine compounds, including cytarabine, eribulin, marizomib, plitidepsin, trabectedin, zalypsis, adcetris, and OKI-179. The future development of anticancer marine drugs requires innovative biochemical biology approaches and introduction of novel therapeutic targets, as well as efficient isolation and synthesis of marine-derived natural compounds and derivatives.
Topics: Animals; Antineoplastic Agents; Biological Products; Humans; Neoplasms; Seawater
PubMed: 34564150
DOI: 10.3390/md19090488 -
Cell Host & Microbe Jun 2018Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided... (Review)
Review
Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided a rich reservoir from which diverse chemical scaffolds could be discovered. Recently, the human microbiome has been recognized as a promising niche from which secondary metabolites with therapeutic potential have begun to be isolated. In this Review, we address how the expansive history of identifying bacterial natural products in other environments is informing the approaches being brought to bear on the study of the human microbiota. We also touch on how these tools can lead to insights about microbe-microbe and host-microbe interactions and help generate biological hypotheses that may lead to developments of new therapeutic modalities.
Topics: Anti-Bacterial Agents; Bacteria; Biological Products; Humans; Indoles; Metabolomics; Metagenomics; Microbial Interactions; Microbiota; Multigene Family; Peptides, Cyclic; Pyrrolidonecarboxylic Acid; Thiazolidines
PubMed: 29902438
DOI: 10.1016/j.chom.2018.05.013 -
Molecules (Basel, Switzerland) Jul 2021Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes... (Review)
Review
Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the , , genera. Corals, , Okinawan/, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing 'compounds' structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognised bioactivity.
Topics: Alkaloids; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Biological Products; Diterpenes; Humans; Toxicity Tests
PubMed: 34279443
DOI: 10.3390/molecules26134103 -
Bioorganic & Medicinal Chemistry Sep 2020Nucleoside derivatives, in particular those featuring uridine, are familiar components of the nucleoside family of bioactive natural products. The structural complexity... (Review)
Review
Nucleoside derivatives, in particular those featuring uridine, are familiar components of the nucleoside family of bioactive natural products. The structural complexity and biological activities of these compounds have inspired research from organic chemistry and chemical biology communities seeking to develop novel approaches to assemble the challenging molecular targets, to gain inspiration for enzyme inhibitor development and to fuel antibiotic discovery efforts. This review will present recent case studies describing the total synthesis and biosynthesis of uridine natural products, and de novo synthetic efforts exploiting features of the natural products to produce simplified scaffolds. This research has culminated in the development of complementary strategies that can lead to effective uridine-based inhibitors and antibiotics. The strengths and challenges of the juxtaposing methods will be illustrated by examining select uridine natural products. Moreover, structure-activity relationships (SAR) for each natural product-inspired scaffold will be discussed, highlighting the impact on inhibitor development, with the aim of future uridine-based small molecule expansion.
Topics: Anti-Bacterial Agents; Biological Products; Drug Discovery; Enzyme Inhibitors; Humans; Molecular Structure; Phosphates; Polyprenols; Structure-Activity Relationship; Uridine
PubMed: 32828427
DOI: 10.1016/j.bmc.2020.115661 -
Molecules (Basel, Switzerland) Dec 2017Reactive Oxygen Species (ROS) are chemically reactive chemical species containing oxygen. The redox status of a cell is function of the relative concentrations of... (Review)
Review
Reactive Oxygen Species (ROS) are chemically reactive chemical species containing oxygen. The redox status of a cell is function of the relative concentrations of oxidized and reduced forms of proteins, enzymes, ROS, molecules containing thiol and other factors. In the organism, the redox balance is based on the generation and elimination of ROS produced by endogenous and exogenous sources. All living organisms must maintain their redox equilibrium to survive and proliferate. Enzymatic and molecular pathways control ROS levels tightly but differentially depending on the type of cell. This review is an overview of various molecules that modulate ROS production/detoxification and have a synergistic action with the chemotherapies to kill cancer cells while preserving normal cells to avoid anticancer drugs side effects, allowing a better therapeutic index of the anticancer treatments.
Topics: Animals; Antineoplastic Agents; Antioxidants; Biological Products; Catalysis; Drug Synergism; Humans; Neoplasms; Oxidation-Reduction; Plant Extracts; Reactive Oxygen Species; Superoxide Dismutase
PubMed: 29301225
DOI: 10.3390/molecules23010084