scholarly journals NATURAL PRODUCTS: FROM TRADITIONAL MEDICINE TO LEAD COMPOUNDS FOR DRUG DEVELOPMENT IN THE 21ST CENTURY

2021 ◽  
pp. 97-104
Author(s):  
Beatriz de las Heras Polo
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
Structural Complexity ◽  
Cost Benefit ◽  
Bioactive Molecules ◽  
Computational Techniques ◽  
Design And Optimization ◽  
Technological Advances ◽  
Biological Tests

Natural products have historically contributed to drug discovery as a source of bioactive molecules, due to their great diversity and structural complexity. They have provided “lead” molecules for the development of drugs in different therapeutic areas, with a very prominent representation in the treatment of pain and inflammation, coagulation disorders, metabolic disorders, as well as in the treatment of cancer and infectious diseases. In recent decades there has been a paradigm shift in drug discovery strategies that has allowed the identification of new active natural products in therapeutic targets. Combinatorial Chemistry and biological tests (High Throughput Screening), together with the development of computational techniques, have contributed decisively to the design and optimization of libraries of natural product derivatives based on their biological activity. In parallel, technological advances in the field of Omics sciences and in data processing lead to a multidimensional approach in the drug discovery process. These powerful tools will allow the analysis of the pharmacological potential of natural products and their derivatives for the conversion of these molecules to active products with low toxicity. In the Precision Medicine era, natural products continue to be molecules with great potential in pharmaceutical development, since, unlike other therapeutic strategies, they have a favorable cost-benefit ratio, which will allow their future use in this discipline.

scholarly journals Novel Natural Product Discovery from Marine Sponges and their Obligate Symbiotic Organisms

2014 ◽  
Author(s):  
Regina Monaco ◽  
Rena Quinlan
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Marine Invertebrates ◽  
Quinone Reductase ◽  
Marine Sponges ◽  
Bioactive Molecules ◽  
Channel Blockers ◽  
Terrestrial Plants ◽  
Technological Advances ◽  
Pharmacologically Active

Abstract: Discovery of novel natural products is an accepted method for the elucidation of pharmacologically active molecules and drug leads. Best known sources for such discovery have been terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use (1), and about 60% of approved pharmaceuticals and new drug applications annually (2). Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Exploration began in earnest in the 1950’s, after technological advances such as scuba diving allowed collection of marine organisms, primarily at a depth to about 15m. Natural products from filter feeding marine invertebrates and in particular, sponges, have proven to be a rich source of structurally unique pharmacologically active compounds, with over 16,000 molecules isolated thus far (3, 1) and a continuing pace of discovery at hundreds of novel bioactive molecules per year. All classes of pharmaceuticals have been represented in this discovery process, including antiprotazoals, pesticides, TGF-beta inhibitors, cationic channel blockers, anticancer, cytotoxic, antiviral, anti-inflammatory and antibacterial compounds. Important biosynthetic pathways found in sponges which give rise to these compounds include the terpenoid (4), fatty acid, polyketoid, quinone reductase, alkaloid, isoprenoid (5), and non-ribosomal protein synthase pathways. Keywords: natural products; marine sponges; drug discovery; terpenoids; carotenoids; polyketides; marine drug discovery

scholarly journals Molecular representations in AI-driven drug discovery: a review and practical guide

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Laurianne David ◽  
Amol Thakkar ◽  
Rocío Mercado ◽  
Ola Engkvist
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
Computational Analysis ◽  
Bioactive Molecules ◽  
Past Century ◽  
Graph Representations ◽  
The Past ◽  
Technological Advances ◽  
Fast Development ◽  
Chemical Representations

Abstract The technological advances of the past century, marked by the computer revolution and the advent of high-throughput screening technologies in drug discovery, opened the path to the computational analysis and visualization of bioactive molecules. For this purpose, it became necessary to represent molecules in a syntax that would be readable by computers and understandable by scientists of various fields. A large number of chemical representations have been developed over the years, their numerosity being due to the fast development of computers and the complexity of producing a representation that encompasses all structural and chemical characteristics. We present here some of the most popular electronic molecular and macromolecular representations used in drug discovery, many of which are based on graph representations. Furthermore, we describe applications of these representations in AI-driven drug discovery. Our aim is to provide a brief guide on structural representations that are essential to the practice of AI in drug discovery. This review serves as a guide for researchers who have little experience with the handling of chemical representations and plan to work on applications at the interface of these fields.

scholarly journals Natural Products as Modulators of Sirtuins

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3287 ◽  
Author(s):  
Berin Karaman Mayack ◽  
Wolfgang Sippl ◽  
Fidele Ntie-Kang
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Histone Deacetylases ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Class Iii ◽  
Drug Candidates ◽  
Starting Point ◽  
Recent Developments ◽  
Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds, as well as the potential application of naturally occurring sirtuin inhibitors in human health and those in clinical trials.

A primer on natural product-based virtual screening

2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Eleni Koulouridi ◽  
Marilia Valli ◽  
Fidele Ntie-Kang ◽  
Vanderlan da Silva Bolzani
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Molecular Modeling ◽  
Virtual Screening ◽  
Natural Product ◽  
General Purpose ◽  
Target Type ◽  
Computational Techniques ◽  
Specific Subset ◽  
Virtual Libraries

Abstract Databases play an important role in various computational techniques, including virtual screening (VS) and molecular modeling in general. These collections of molecules can contain a large amount of information, making them suitable for several drug discovery applications. For example, vendor, bioactivity data or target type can be found when searching a database. The introduction of these data resources and their characteristics is used for the design of an experiment. The description of the construction of a database can also be a good advisor for the creation of a new one. There are free available databases and commercial virtual libraries of molecules. Furthermore, a computational chemist can find databases for a general purpose or a specific subset such as natural products (NPs). In this chapter, NP database resources are presented, along with some guidelines when preparing an NP database for drug discovery purposes.

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

scholarly journals Emerging Optical Materials in Sensing and Discovery of Bioactive Compounds

Sensors ◽  
2021 ◽  
Vol 21 (17) ◽  
pp. 5784
Author(s):  
Raquel Vaz ◽  
Beatriz Valpradinhos ◽  
Manuela F. Frasco ◽  
Maria Goreti F. Sales
Keyword(s):  
Drug Discovery ◽  
Bioactive Compounds ◽  
High Throughput Screening ◽  
High Sensitivity ◽  
Optical Biosensors ◽  
Chemical Compositions ◽  
Bioactive Natural Products ◽  
Real Time Analysis ◽  
Technological Advances ◽  
Recent Developments

Optical biosensors are used in numerous applications and analytical fields. Advances in these sensor platforms offer high sensitivity, selectivity, miniaturization, and real-time analysis, among many other advantages. Research into bioactive natural products serves both to protect against potentially dangerous toxic compounds and to promote pharmacological innovation in drug discovery, as these compounds have unique chemical compositions that may be characterized by greater safety and efficacy. However, conventional methods for detecting these biomolecules have drawbacks, as they are time-consuming and expensive. As an alternative, optical biosensors offer a faster, simpler, and less expensive means of detecting various biomolecules of clinical interest. In this review, an overview of recent developments in optical biosensors for the detection and monitoring of aquatic biotoxins to prevent public health risks is first provided. In addition, the advantages and applicability of these biosensors in the field of drug discovery, including high-throughput screening, are discussed. The contribution of the investigated technological advances in the timely and sensitive detection of biotoxins while deciphering the pathways to discover bioactive compounds with great health-promoting prospects is envisaged to meet the increasing demands of healthcare systems.

Novel natural product discovery from obligate symbiotic organisms of marine sponges

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Regina R. Monaco ◽  
Rena F. Quinlan
Keyword(s):  
Natural Products ◽  
Marine Invertebrates ◽  
Quinone Reductase ◽  
Marine Sponges ◽  
Rich Source ◽  
Bioactive Molecules ◽  
Channel Blockers ◽  
Terrestrial Plants ◽  
Technological Advances ◽  
Pharmacologically Active

A rich source for the discovery of novel, pharmacologically active natural products has been terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use (1), and about 60% of approved pharmaceuticals and new drug applications annually (2). Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Such exploration began in the 1950’s, after technological advances such as scuba diving allowed collection of marine organisms, primarily to a depth of about 15m, which was the limit of that technology.Natural products from filter feeding marine invertebrates and in particular, sponges, have proven to be a rich source of structurally unique pharmacologically active compounds, with over 16,000 molecules isolated thus far (3, 1) and a continuing pace of discovery at hundreds of novel bioactive molecules per year. All classes of pharmaceuticals have been represented in this discovery process, including antiprotozoals, pesticides, TGF-beta inhibitors, cationic channel blockers, anticancer, cytotoxic, antiviral, anti-inflammatory and antibacterial compounds. Important biosynthetic pathways found in sponges which give rise to these compounds include the terpenoid (4), fatty acid, polyketoid, quinone reductase, alkaloid, isoprenoid (5), and non-ribosomal protein synthase pathways.

scholarly journals Natural Products as Modulators of Sirtuins

2020 ◽  
Author(s):  
Berin Karaman Mayack ◽  
Wolfgang Sippl ◽  
Fidele Ntie-Kang
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Histone Deacetylases ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Class Iii ◽  
Drug Candidates ◽  
Starting Point ◽  
Recent Developments ◽  
Potent Drug

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as Sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of Sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds.

Changing paradigm for drug development: A case study of natural products

2011 ◽  
Vol 83 (9) ◽  
pp. 1643-1650
Author(s):  
◽  
M. Iqbal Choudhary ◽  
Naik Tameen Khan
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput Screening ◽  
Cost Effective ◽  
Optimization Techniques ◽  
Lead Discovery ◽  
Biological Targets ◽  
Sar Studies ◽  
Glucosidase Inhibitors

Natural products have been a rich source of lead identification for drug discovery and development. Over the last two decades, the impetus for natural product-based lead discovery in pharmaceutical industry has declined, resulting in a productivity and innovation crisis. Most of the focus is now on high-throughput screening of synthetic libraries of compounds against defined biological targets; however, discovery of new molecular entities (NMEs) is still declining in this postgenomic era. With the availability of modern purification, characterization, and yield optimization techniques, and with an established intellectual property rights (IPR) regime, it is now possible to circumvent the problems once associated with natural product-based drug discovery. Our work demonstrates that natural products can lead to cost-effective identification of lead molecules against a defined molecular target. During our recent studies, novel classes of urease and α-glucosidase inhibitors were initially obtained from medicinal plants, and based on these novel structural leads, synthetic libraries of structural analogues were synthesized for structure–activity relationship (SAR) studies. These synthetic analogues have shown potent inhibitory activities against the target enzymes, and their mechanisms of action were studied by kinetic, computational, and NMR-based methods.

scholarly journals Design and Synthesis of Anti-Cancer Chimera Molecules Based on Marine Natural Products

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 500 ◽  
Author(s):  
Min Woo Ha ◽  
Bo Reum Song ◽  
Hye Jin Chung ◽  
Seung-Mann Paek
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Structural Complexity ◽  
Biological Evaluation ◽  
Bioactive Molecules ◽  
Severe Toxicity ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Cancer Agent

In this paper, the chemical conjugation of marine natural products with other bioactive molecules for developing an advanced anti-cancer agent is described. Structural complexity and the extraordinary biological features of marine natural products have led to tremendous research in isolation, structural elucidation, synthesis, and pharmacological evaluation. In addition, this basic scientific achievement has made it possible to hybridize two or more biologically important skeletons into a single compound. The hybridization strategy has been used to identify further opportunities to overcome certain limitations, such as structural complexity, scarcity problems, poor solubility, severe toxicity, and weak potency of marine natural products for advanced development in drug discovery. Further, well-designed marine chimera molecules can function as a platform for target discovery or degradation. In this review, the design, synthesis, and biological evaluation of recent marine chimera molecules are presented.

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