Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone?A.

ABSTRACT: Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone?A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.

SUBMITTER: Mills JJ

PROVIDER: S-EPMC6033662 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A.

Mills Jonathan J JJ Robinson Kaylib R KR Zehnder Troy E TE Pierce Joshua G JG

Angewandte Chemie (International ed. in English) 20180610 28

Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues t ...[more]

PMID: 29845720

Similar Datasets

Family-level stereoselective synthesis and biological evaluation of pyrrolomorpholine spiroketal natural product antioxidants.

Project description:The pyranose spiroketal natural products pollenopyrroside A and shensongine A (also known as xylapyrroside A, ent-capparisine B) have been synthesized by stereoselective spirocyclizations of a common C1-functionalized glycal precursor. In conjunction with our previously reported syntheses of the corresponding furanose isomers, this provides a versatile family-level synthesis of the pyrrolomorpholine spiroketal natural products and analogues. In rat mesangial cells, hyperglycemia-induced production of reactive oxygen species, which is implicated in diabetic nephropathy, was inhibited by pollenopyrroside A and shensongine A with mid-?M IC50 values, while unnatural C2-hydroxy analogues exhibited more potent, sub-?M activity.

| S-EPMC5571482 | biostudies-literature

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers.

Project description:The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.

| S-EPMC4737532 | biostudies-literature

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

Project description:Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

| S-EPMC4797711 | biostudies-other

Total Synthesis and Biological Evaluation of Apratoxin E and Its C30 Epimer: Configurational Reassignment of the Natural Product.

Project description:Apratoxin E provided the inspiration for the design of apratoxin A/E hybrids under preclinical development. Through total synthesis using two different strategies, it was determined that the originally proposed configuration of the thiazoline at C30 is opposite from that in apratoxin A, in contrast to previous assumptions on biosynthetic grounds. The epimer and true natural apratoxin E were synthesized, and the biological activities were evaluated.

| S-EPMC5386831 | biostudies-literature

Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product.

Project description:Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties.

| S-EPMC1462728 | biostudies-literature

Stereoselective Synthesis of the Isomers of Notoincisol A: Assigment of the Absolute Configuration of this Natural Product and Biological Evaluation.

Project description:The total syntheses of all stereoisomers of notoincisol A, a recently isolated natural product with potential anti-inflammatory activity, are reported. The asymmetric synthesis was conducted employing a lipase-mediated kinetic resolution, which enables easy access to all required chiral building blocks with the aim of establishing the absolute configuration of the naturally occurring isomer. This was achieved by comparison of optical properties of the isolated compound with the synthetic derivatives obtained. Moreover, an assessment of the biological activity on PPAR? (peroxisome proliferator-activated receptor gamma) as a prominent receptor related to inflammation is reported. Only the natural isomer was found to activate the PPAR? receptor, and this phenomenon could be explained based on molecular docking studies. In addition, the pharmacological profiles of the isomers were determined using the GABAA (gamma-aminobutyric acid A) ion channel receptor as a representative target for allosteric modulation related to diverse CNS activities. These compounds were found to be weak allosteric modulators of the ?1?3 and ?1?2?2 receptor subtypes.

| S-EPMC6256351 | biostudies-literature

Synthesis and biological evaluation of 5,7-dihydroxyflavanone derivatives as antimicrobial agents.

Project description:A series of 5,7-dihydroxyflavanone derivatives were efficiently synthesized. Their antimicrobial efficacy on Gram-negative, Gram-positive bacteria and yeast were evaluated. Among these compounds, most of the halogenated derivatives exhibited the best antimicrobial activity against Gram-positive bacteria, the yeast Saccharomyces cerevisiae, and the Gram-negative bacterium Vibrio cholerae. The cytotoxicities of these compounds were low as evaluated on HepG2 cells using a cell viability assay. This study suggests that halogenated flavanones might represent promising pharmacological candidates for further drug development.

| S-EPMC7927313 | biostudies-literature

Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens.

Project description:Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise. Herein, we report the total synthesis of natural albomycins ?1 (1a), ?2 (1b), and ? (1c), which validates the structures of these peptidylnucleoside compounds and allows for synthetic access to bioactive albomycin analogs. The efficient synthesis of albomycins enables extensive evaluations of these natural products against model bacteria and clinical pathogens. Albomycin ?2 has the potential to be developed into an antibacterial drug to treat Streptococcus pneumoniae and Staphylococcus aureus infections.

| S-EPMC6123416 | biostudies-literature

Identification of a Pantoea biosynthetic cluster that directs the synthesis of an antimicrobial natural product.

Project description:Fire Blight is a destructive disease of apple and pear caused by the enteric bacterial pathogen, Erwinia amylovora. E. amylovora initiates infection by colonizing the stigmata of apple and pear trees, and entering the plants through natural openings. Epiphytic populations of the related enteric bacterium, Pantoea, reduce the incidence of disease through competition and antibiotic production. In this study, we identify an antibiotic from Pantoea ananatis BRT175, which is effective against E. amylovora and select species of Pantoea. We used transposon mutagenesis to create a mutant library, screened approximately 5,000 mutants for loss of antibiotic production, and recovered 29 mutants. Sequencing of the transposon insertion sites of these mutants revealed multiple independent disruptions of an 8.2 kb cluster consisting of seven genes, which appear to be coregulated. An analysis of the distribution of this cluster revealed that it was not present in any other of our 115 Pantoea isolates, or in any of the fully sequenced Pantoea genomes, and is most closely related to antibiotic biosynthetic clusters found in three different species of Pseudomonas. This identification of this biosynthetic cluster highlights the diversity of natural products produced by Pantoea.

| S-EPMC4010436 | biostudies-literature

Efforts To Access the Potent Antitrypanosomal Marine Natural Product Janadolide: Synthesis of Des-<i>tert</i>-butyl Janadolide and Its Biological Evaluation.

Project description:To identify novel antitrypanosomal agents based on Janadolide, a potent macrocyclic polyketide-peptide hybrid, a macrolactonization strategy was explored. We prepared des-tert-butyl Janadolide and evaluated its antitrypanosomal activity. Our findings suggest that the tert-butyl group is necessary for the desired bioactivity.

| S-EPMC6044843 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data