Natural products as lead compounds in drug discovery

AbstractFor the past 2 years, the coronavirus responsible for the COVID-19 infection has become a world pandemic, ruining the lives and economies of several nations in the world. This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies. Natural products are known to be a rich source of lead compounds for drug discovery, including against infectious diseases caused by microbes (viruses, bacteria and fungi). In this review article, we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins, which lie below 10 µM. This led to the identification of 42 compounds belonging to the alkaloid, flavonoid, terpenoid, phenolic, xanthone and saponin classes. The cut off concentration of 10 µM was to limit the study to the most potent chemical entities, which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.

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A stereolibrary of conformationally restricted amino acids based on pyrrolidinyl/piperidinyloxazole motifs

Heterocyclic Communications ◽

10.1515/hc-2015-0137 ◽

2015 ◽

Vol 21 (6) ◽

pp. 391-395 ◽

Cited By ~ 1

Author(s):

Oleksiy S. Artamonov ◽

Taras Bulda ◽

Tkhe Kyong Fam ◽

Evgeniy Y. Slobodyanyuk ◽

Dmitry M. Volochnyuk ◽

...

Keyword(s):

Amino Acids ◽

Natural Products ◽

Drug Discovery ◽

Carboxylic Acids ◽

Building Blocks ◽

Conformationally Restricted ◽

Lead Compounds ◽

Restricted Amino Acids

AbstractA stereolibrary of conformationally restricted oxazole-containing amino acids, namely all isomers of 5–pyrrolydinyl- and 5-piperidinyloxazole-4-carboxylic acids, were designed and synthesized in three steps by the reaction of the corresponding N-Boc-protected amino acids and ethyl isocyanoacetate. These natural products-inspired amino acids are valuable building blocks for the synthesis of peptidomimetics and potential lead compounds for drug discovery.

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Recent Applications of Benzimidazole as a Privileged Scaffold in Drug Discovery

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200804124924 ◽

2020 ◽

Vol 20 ◽

Author(s):

Yongzhen Guo ◽

Xuben Hou ◽

Hao Fang

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Anticancer Agents ◽

Medicinal Chemistry ◽

Biological Activities ◽

Great Influence ◽

Parasitic Infections ◽

Peptic Ulcers ◽

Lead Compounds ◽

Privileged Scaffold

: Benzimidazole is an aromatic bicyclic heterocycle that is regarded as a valuable privileged scaffold in medicinal chemistry. Many marketed drugs and natural products containing benzimidazole scaffolds exert great influence in fighting various diseases, such as hypertension, peptic ulcers, parasitic infections, and cancer. In this review, we introduce the pharmacological applications of some marketed drugs and lead compounds with a focus on anticancer agents, reporting the corresponding data to show the biological activities at their targets. The publications in this review encompass those from 2014 to 2019.

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Metabolomics in the Context of Plant Natural Products Research: From Sample Preparation to Metabolite Analysis

Metabolites ◽

10.3390/metabo10010037 ◽

2020 ◽

Vol 10 (1) ◽

pp. 37 ◽

Cited By ~ 11

Author(s):

Mohamed A. Salem ◽

Leonardo Perez de Souza ◽

Ahmed Serag ◽

Alisdair R. Fernie ◽

Mohamed A. Farag ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Sample Preparation ◽

Plant Sample ◽

Lead Compounds ◽

Natural Extracts ◽

Plant Natural Products ◽

Single Compound ◽

Indispensable Tool ◽

Complex Chemistry

Plant-derived natural products have long been considered a valuable source of lead compounds for drug development. Natural extracts are usually composed of hundreds to thousands of metabolites, whereby the bioactivity of natural extracts can be represented by synergism between several metabolites. However, isolating every single compound from a natural extract is not always possible due to the complex chemistry and presence of most secondary metabolites at very low levels. Metabolomics has emerged in recent years as an indispensable tool for the analysis of thousands of metabolites from crude natural extracts, leading to a paradigm shift in natural products drug research. Analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are used to comprehensively annotate the constituents of plant natural products for screening, drug discovery as well as for quality control purposes such as those required for phytomedicine. In this review, the current advancements in plant sample preparation, sample measurements, and data analysis are presented alongside a few case studies of the successful applications of these processes in plant natural product drug discovery.

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Marine Actinomycetes-derived Natural Products

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191114102359 ◽

2020 ◽

Vol 19 (31) ◽

pp. 2868-2918 ◽

Cited By ~ 3

Author(s):

Chengfang Yang ◽

Rui Qian ◽

Yao Xu ◽

Junxi Yi ◽

Yiwen Gu ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Secondary Metabolites ◽

Metabolic Pathways ◽

Biological Activities ◽

Living Environment ◽

Marine Actinomycetes ◽

Bioactive Substances ◽

Lead Compounds

: Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.

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Exploring Chemical Diversity of Phorbas Sponges as a Source of Novel Lead Compounds in Drug Discovery

10.20944/preprints202110.0354.v1 ◽

2021 ◽

Author(s):

Alessia Caso ◽

Fernanda Barbosa da Silva ◽

Germana Esposito ◽

Roberta Teta ◽

Gerardo Della Sala ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Secondary Metabolites ◽

Marine Natural Products ◽

Biological Activities ◽

Great Majority ◽

Marine Sponges ◽

Chemical Diversity ◽

Lead Compounds ◽

Anti Inflammatory

Porifera, commonly referred to as marine sponges, have stood out as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention along years. They are widespread in all continents, and several structurally unique compounds have been identified from species of this genus. Terpenes, mainly sesterterpenoids, represent the great majority of secondary metabolites isolated from Phorbas species, even though several alkaloids and steroids have also been reported. Many of these compounds have shown a variety of biological activities. Particularly, Phorbas sponges have been demonstrated to be a source of cytotoxic metabolites. In addition, MNPs exhibiting cytostatic, antimicrobial and anti-inflammatory activities, have been isolated and structurally characterized. This work brings an overview of Phorbas secondary metabolites reported since the first study published in 1993 until 2020, and their biological activities.

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Exploring Chemical Diversity of Phorbas Sponges as a Source of Novel Lead Compounds in Drug Discovery

Marine Drugs ◽

10.3390/md19120667 ◽

2021 ◽

Vol 19 (12) ◽

pp. 667

Author(s):

Alessia Caso ◽

Fernanda Barbosa da Silva ◽

Germana Esposito ◽

Roberta Teta ◽

Gerardo Della Sala ◽

...

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Secondary Metabolites ◽

Marine Natural Products ◽

Biological Activities ◽

Marine Sponges ◽

Chemical Diversity ◽

Lead Compounds ◽

Synthetic Routes ◽

Anti Inflammatory

Porifera, commonly referred to as marine sponges, are acknowledged as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention over the years. They are widespread in all continents, and several structurally unique compounds have been identified from this species. Terpenes, mainly sesterterpenoids, are the major secondary metabolites isolated from Phorbas species, even though several alkaloids and steroids have also been reported. Many of these compounds have presented interesting biological activities. Particularly, Phorbas sponges have been demonstrated to be a source of cytotoxic metabolites. In addition, MNPs exhibiting cytostatic, antimicrobial, and anti-inflammatory activities have been isolated and structurally characterized. This review provides an overview of almost 130 secondary metabolites from Phorbas sponges and their biological activities, and it covers the literature since the first study published in 1993 until November 2021, including approximately 60 records. The synthetic routes to the most interesting compounds are briefly outlined.

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Osthole: A Promising Lead Compound for Drug Discovery from a Traditional Chinese Medicine (TCM)

Natural Product Communications ◽

10.1177/1934578x0900400227 ◽

2009 ◽

Vol 4 (2) ◽

pp. 1934578X0900400 ◽

Cited By ~ 3

Author(s):

Lisha You ◽

Song Feng ◽

Rui An ◽

Xinhong Wang

Keyword(s):

Natural Products ◽

Drug Discovery ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Pharmaceutical Compounds ◽

Therapeutic Agents ◽

Biological Information ◽

Lead Compound ◽

Pharmacological Activities ◽

Lead Compounds

Natural products have always been important resources either as therapeutic agents or as lead compounds for the production of pharmaceutical compounds. Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, an ingredient of a Traditional Chinese Medicine(TCM), has received considerable attention recently because of its significant and diverse pharmacological activities, including anticancer, antisteoporotic, and antiproliferative, which make it a very promising natural lead compound for new drug discovery. The present work summarizes the related biological information on osthole and its analogues and proposes the possibility of its development as a promising lead compound for drug discovery.

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