Browse
Submit Data
Databases
API
Help

Dataset Information

33 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and antifungal activity of natural product-based 6-alkyl-2,3,4,5-tetrahydropyridines.

ABSTRACT: Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a-5g) that mimic the natural piperideines that were recently identified in fire ant venom have been synthesized. Compounds 5c-5g with C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active. Compound 5e exhibited minimum fungicidal concentrations of 3.8, 15.0, 7.5, and 7.5 ?g/mL against Cryptococcus neoformans, Candida albicans, Candida glabrata, and Candida krusei, respectively. The antifungal activities of these compounds appear to be associated with the C-6 side chain length. This study represents the first effort to evaluate antifungal activities of synthetic analogues of the newly identified fire ant venom alkaloids.

SUBMITTER: Dai L

PROVIDER: S-EPMC3189850 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and antifungal activity of natural product-based 6-alkyl-2,3,4,5-tetrahydropyridines.

Dai Liyan L Jacob Melissa R MR Khan Shabana I SI Khan Ikhlas A IA Clark Alice M AM Li Xing-Cong XC

Journal of natural products 20110909 9

Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a-5g) that mimic the natural piperideines that were recently identified in fire ant venom have been synthesized. Compounds 5c-5g with C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active. Compound 5e exhibited minimum fungicidal concentrations of 3.8, 15.0, 7.5, and 7.5 μg/mL against Cryptococcus ne ...[more]

PMID: 21905650

Similar Datasets

Concise Total Synthesis and Antifungal Activities of Fusaric Acid, a Natural Product.

Project description:The total synthesis of a natural product alkaloid fusaric acid (FA), which exhibits herbicide, fungicide, insecticide and even diverse notable pharmacological activities, was accomplished in four steps using commercially available materials. The synthesis, based on a unified and flexible strategy using 6-bromonicotinaldehyde as a common intermediate, is concise, convergent, practical and can be carried out on a two-gram scale. This approach could be readily applicable to the synthesis of its analogues. In addition, FA had a wide range of inhibitory activities against 14 plant pathogenic fungi in this study, which demonstrated that as a leading compound, and it has great potential to be further developed as an agricultural fungicide.

| S-EPMC7503603 | 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 structure-activity investigation of the marine natural product neopeltolide.

Project description:The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.

| S-EPMC2735232 | biostudies-literature

A landmark in drug discovery based on complex natural product synthesis.

Project description:Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.

| S-EPMC6572832 | biostudies-literature

Natural Product Based 6-Hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium Scaffold as A New Antifungal Template.

Project description:Synthetic analogues of the marine-derived class of natural products phloeodictines have been prepared and exhibited potent in vitro fungicidal activities against a broad array of fungal pathogens including drug resistant strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural moiety with a C12 to C16 aliphatic side chain at C-6 has been shown to be the antifungal pharmacophore and may serve as a new antifungal template for further lead optimization.

| S-EPMC3129868 | biostudies-literature

Design, synthesis and hepatoprotective activity of analogs of the natural product goodyeroside A.

Project description:Goodyeroside A, a natural product isolated from the Goodyera species, possesses significant hepatoprotective activity and has a novel skeleton not previously observed in other synthetic drugs used for the treatment of hepatitis. Herein, we report a highly stereoselective synthesis of goodyeroside A and related analogs with varying substituents at the α position of the carbonyl group to explore the structure-activity relationships of goodyeroside A. The absolute configuration of analog 5d was confirmed by single crystal X-ray analysis. The results from in vitro and in vivo studies indicate that 5a, the fully acetylated compound of goodyeroside A, is worthy of further investigation as a lead to identify novel hepatoprotective agents.

| S-EPMC6269934 | biostudies-literature

Synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold.

Project description:A short practical synthesis of a new natural product based scaffold (6), based on antitrypanosomal and antimalarial compounds isolated from different Plakortis species is described. The scaffold contains a peroxide unit that is surprisingly stable to chemical manipulation elsewhere in the molecule, enabling it to be elaborated into a small library of derivatives. It is stable to ozonolysis, reductive work-up with dimethylsulfide and the Wittig reaction with stabilized phosphorus ylides. The scaffold along with its Wittig analogues has displayed low to sub-micro molar (0.2-3.3 ?M) antitrypanosomal activity.

| S-EPMC3228865 | biostudies-literature

Investigating the mechanism by which the natural product compound puupehenone potentiates the antifungal drug caspofungin

Project description:The cell wall-targeting echinocandin antifungals, although potent and well-tolerated, are inadequate in treating fungal infections due to their narrow spectrum of activity and their propensity to induce pathogen resistance. A promising strategy to overcome these drawbacks is to combine echinocandins with a molecule that improves their activity and also disrupts drug adaptation pathways. In this study, we show that puupehenone (PUUP), a marine sponge-derived sesquiterpene quinone potentiates the echinocandin drug, caspofungin (CAS) in CAS-resistant fungal pathogens. We have conducted RNA-Seq analysis, followed by genetic and molecular studies, to elucidate PUUP’s CAS-potentiating mechanism. We found that the combination of CAS and PUUP blocked the induction of CAS-responding genes required for the adaptation to cell wall stress through the cell wall integrity (CWI) pathway. Further analysis showed that PUUP inhibited the activation of Slt2 (Mpk1), the terminal MAP kinase in this pathway. We also found that PUUP induced heat shock response genes and inhibited the activity of heat shock protein 90 (Hsp90). Molecular docking studies predicted that PUUP occupies a binding site on Hsp90 required for the interaction between Hsp90 and its co-chaperone Cdc37. Thus, we show that PUUP potentiates CAS activity by a previously undescribed mechanism which involves disruption of Hsp90 activity and the CWI pathway. Given the requirement of the Hsp90-Cdc37 complex in Slt2 activation, we suggest that inhibitors of this complex would disrupt the CWI pathway and synergize with echinocandins. Therefore, the identification of PUUP’s CAS-potentiating mechanism has important implications in the development of new antifungal combination therapies.

2019-12-04 | GSE140563 | GEO

Synthesis and anti-tuberculosis activity of the marine natural product caulerpin and its analogues.

Project description:Caulerpin (1a), a bis-indole alkaloid from the marine algal Caulerpa sp., was synthesized in three reaction steps with an overall yield of 11%. The caulerpin analogues (1b-1g) were prepared using the same synthetic pathway with overall yields between 3% and 8%. The key reaction involved a radical oxidative aromatic substitution involving xanthate (3) and 3-formylindole compounds (4a-4g). All bis-indole compounds synthesized were evaluated against the Mycobacterium tuberculosis strain H37Rv, and 1a was found to display excellent activity (IC?? 0.24 µM).

| S-EPMC4012461 | biostudies-literature

Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity.

Project description:A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.

| S-EPMC5488202 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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