Natural products as lead structures: chemical transformations to create lead-like libraries

Pascolutti, Mauro; Quinn, Ronald J.

doi:10.1016/j.drudis.2013.10.013

Cited by 95 publications

(60 citation statements)

References 59 publications

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“…The tetramates and piperidinediones reported herein provide synthetically accessible but unusual systems worthy of further investigation, for which suitable optimisation might provide a novel approach for the treatment of bacterial infections 63. These results further demonstrate the use of natural products as lead structures with biologically validated starting points for drug discovery, as has been promoted by Newman,64 Waldemann65–67 and Quinn 68. 69…”

Section: Discussionsupporting

confidence: 52%

A Detailed Study of Antibacterial 3‐Acyltetramic Acids and 3‐Acylpiperidine‐2,4‐diones

Jeong

Bikádi²,

Hazai³

et al. 2014

ChemMedChem

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Inspired by the core fragment of antibacterial natural products such as streptolydigin, 3-acyltetramic acids and 3-acylpiperidine-2,4-diones have been synthesised from the core heterocycle by direct acylation with the substituted carboxylic acids using a strategy which permits ready access to a structurally diverse compound library. The antibacterial activity of these systems has been established against a panel of Gram-positive and Gram-negative bacteria, with activity mostly against the former, which in some cases is very potent. Data consistent with modes of action against undecaprenylpyrophosphate synthase (UPPS) and/or RNA polymerase (RNAP) for a small subset of the library has been obtained. The most active compounds have been shown to exhibit binding at known binding sites of streptolydigin and myxopyronin at UPPS and RNAP. These systems offer potential for their antibacterial activity, and further demonstrate the use of natural products as biologically validated starting points for drug discovery.

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Section: Discussionsupporting

confidence: 52%

A Detailed Study of Antibacterial 3‐Acyltetramic Acids and 3‐Acylpiperidine‐2,4‐diones

Jeong

Bikádi²,

Hazai³

et al. 2014

ChemMedChem

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“…According to the World Health Organization approximately 80% of the world's population uses traditional medicines in its primary healthcare [1,2]. Nature is equally important for the healthcare systems of developed countries, since almost 25% of the prescribed drugs contain plant extracts or metabolites and an additional significant percentage of the commercial drugs has been developed through studies employing natural products as the lead molecules [3,4].…”

Section: Introductionmentioning

confidence: 99%

The Laurencia Paradox: An Endless Source of Chemodiversity

Harizani

Iοannou

Roussis

2016

Progress in the Chemistry of Organic Natural Products 102

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Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites.

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“…The HMBC correlations between H-3 (δ H 5.83) and C-1 (δ C 79.3), C-4 (δ C 187.0), and C-5 (δ C 61.0), together with the correlations between H-15 (δ H 1.03) and H-16 (δ H 1.28) and C-1, C-7 (δ C 43.1), and C-8 (δ C 44.9), plus the correlations between gem H-6 (δ H 1.47, 1.83) and C-4, C-5, C-7, C-8, and C-9 (δ C 209.4), support the bicyclo[3.3.1]nonane-2,4,9-trione system of garcicosin (1). The geranyl unit was clearly established by COSY, HSQC, and HMBC correlations (see Table 1 and Supporting information).…”

mentioning

confidence: 77%

A New Polycyclic Polyprenylated Acylphloroglucinol Derivative from Garcinia verrucosa

Rajaonarivelo

Rakotonandrasana

Martin

et al. 2016

Natural Product Communications

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In our continuing phytochemical screening program aimed at finding major constituents of endemic Madagascar plants as potential templates for semisynthesis, we investigated the ethyl acetate extract of stem bark of Garcinia verrucosa. Fractionation of the extract led to the isolation of the major compound named garcicosin. Its structure was elucidated by spectroscopic methods including 1D and 2D homo-and heteronuclear NMR techniques (COSY, HSQC, HMBC and NOESY), and HR-mass spectrometry.

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Natural products as lead structures: chemical transformations to create lead-like libraries

Cited by 95 publications

References 59 publications

A Detailed Study of Antibacterial 3‐Acyltetramic Acids and 3‐Acylpiperidine‐2,4‐diones

A Detailed Study of Antibacterial 3‐Acyltetramic Acids and 3‐Acylpiperidine‐2,4‐diones

The Laurencia Paradox: An Endless Source of Chemodiversity

A New Polycyclic Polyprenylated Acylphloroglucinol Derivative from Garcinia verrucosa

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