Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structure activity relationship study of Mezzettiasides natural products and their four new disaccharide analogues for anticancer/antibacterial activity.

ABSTRACT: Ten members of the mezzettiaside family of natural products were synthesized and evaluated for anticancer and antibacterial activity. Complete anticancer (H460) and antibacterial (B. subtilis) activities for the ten natural products and four new analogues were found. Comparison to the cleistrioside and cleistetroside classes of natural products were made.

SUBMITTER: Bajaj SO

PROVIDER: S-EPMC4338990 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Structure activity relationship study of Mezzettiasides natural products and their four new disaccharide analogues for anticancer/antibacterial activity.

Bajaj Sumit O SO Shi Pei P Beuning Penny J PJ O'Doherty George A GA

MedChemComm 20140801 8

Ten members of the mezzettiaside family of natural products were synthesized and evaluated for anticancer and antibacterial activity. Complete anticancer (H460) and antibacterial (<i>B. subtilis</i>) activities for the ten natural products and four new analogues were found. Comparison to the cleistrioside and cleistetroside classes of natural products were made. ...[more]

PMID: 25729554

Similar Datasets

Structure Activity Relationship Study of the Cleistriosides and Cleistetrosides for Antibacterial/Anticancer Activity.

Project description:Two known cleistriosides and six known cleistetrosides were synthesized and evaluated for anticancer and antibacterial activity. This study, for the first time, reports anticancer activity and comprehensively the antibacterial activity for these oligosaccharide natural products. In addition, two new unnatural cleistetroside analogues were synthesized and tested. Biological activities for the ten oligosaccharides against B. subtilis were found to range between 4 and >64 µM, and for NCI-H460 human lung cancer epithelial cells between 7.5 and 90.9 µM. Similar activities were found for seven of the oligosaccharides against the NCI panel of 60 cell lines. The degree of acylation and location of the specific acetate groups had significant effects on the anticancer and antibacterial activity of both the cleistriosides and cleistetrosides.

| S-EPMC3610185 | biostudies-literature

Chemical Synthesis and Structure-Activity Relationship Study Yield Desotamide a Analogues with Improved Antibacterial Activity.

Project description:Desotamides A, a cyclohexapeptide produced by the deep-sea-derived Streptomyces scopuliridis SCSIO ZJ46, displays notable antibacterial activities against strains of Streptococcus pnuemoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis (MRSE). In this study, to further explore its antibacterial potential and reveal the antibacterial structure-activity relationship of desotamides, 13 cyclopeptides including 10 new synthetic desotamide A analogues and wollamides B/B1/B2 were synthesized and evaluated for their antibacterial activities against a panel of Gram-positive and -negative pathogens. The bioactivity data reveal that residues at position II and VI greatly impact antibacterial activity. The most potent antibacterial analogues are desotamide A4 (13) and A6 (15) where l-allo-Ile at position II was substituted with l-Ile and Gly at position VI was simultaneously replaced by d-Lys or d-Arg; desotamides A4 (13) and A6 (15) showed a 2-4-fold increase of antibacterial activities against a series of Gram-positive pathogens including the prevalent clinical drug-resistant pathogen methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 8-32 μg/mL compared to the original desotamide A. The enhanced antibacterial activity, broad antibacterial spectrum of desotamides A4 and A6 highlighted their potential as new antibiotic leads for further development.

| S-EPMC8225045 | biostudies-literature

Isatin Derived Spirocyclic Analogues with ?-Methylene-?-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.

Project description:Design, synthesis, and evaluation of ?-methylene-?-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNF?-induced NF-?B activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-?M potency. Our data suggest that an isatin-derived spirocyclic ?-methylene-?-butyrolactone is a suitable core for optimization to identify novel anticancer agents.

| S-EPMC5273401 | biostudies-literature

Antibacterial barbituric acid analogues inspired from natural 3-acyltetramic acids; synthesis, tautomerism and structure and physicochemical property-antibacterial activity relationships.

Project description:The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less lipophilic character, with physicochemical properties and ionic states that are similar to current antibiotic agents for oral and injectable use. Unfortunately, the reduction of plasma protein affinity by the barbituric core is not sufficient to achieve activity in vivo. Further optimization to reduce plasma protein affinity and/or elevate antibiotic potency is therefore required, but we believe that these systems offer unusual opportunities for antibiotic drug discovery.

| S-EPMC6272196 | biostudies-other

Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products.

Project description:Backgroundthe proviral insertion site of Moloney murine leukemia (PIM) 1 kinase has served as a therapeutic target for various human cancers due to the enhancement of cell proliferation and the inhibition of apoptosis.Methodsto identify effective PIM1 kinase inhibitors, structure-based virtual screening of natural products of plant origin and de novo design were carried out using the protein-ligand binding free energy function improved by introducing an adequate dehydration energy term.Resultsas a consequence of subsequent enzyme inhibition assays, four classes of PIM1 kinase inhibitors were discovered, with the biochemical potency ranging from low-micromolar to sub-micromolar levels. The results of extensive docking simulations showed that the inhibitory activity stemmed from the formation of multiple hydrogen bonds in combination with hydrophobic interactions in the ATP-binding site. Optimization of the biochemical potency by chemical modifications of the 2-benzylidenebenzofuran-3(2H)-one scaffold led to the discovery of several nanomolar inhibitors with antiproliferative activities against human breast cancer cell lines.Conclusionsthese new PIM1 kinase inhibitors are anticipated to serve as a new starting point for the development of anticancer medicine.

| S-EPMC8003278 | biostudies-literature

Bacterial Natural Disaccharide (Trehalose Tetraester): Molecular Modeling and in Vitro Study of Anticancer Activity on Breast Cancer Cells.

Project description:Isolation and characterization of new biologically active substances affecting cancer cells is an important issue of fundamental research in biomedicine. Trehalose lipid was isolated from Rhodococcus wratislaviensis strain and purified by liquid chromatography. The effect of trehalose lipid on cell viability and migration, together with colony forming assays, were performed on two breast cancer (MCF7-low metastatic; MDA-MB231-high metastatic) and one "normal" (MCF10A) cell lines. Molecular modeling that details the structure of the neutral and anionic form (more stable at physiological pH) of the tetraester was carried out. The tentative sizes of the hydrophilic (7.5 Å) and hydrophobic (12.5 Å) portions of the molecule were also determined. Thus, the used trehalose lipid is supposed to interact as a single molecule. The changes in morphology, adhesion, viability, migration, and the possibility of forming colonies in cancer cell lines induced after treatment with trehalose lipid were found to be dose and time dependent. Based on the theoretical calculations, a possible mechanism of action and membrane asymmetry between outer and inner monolayers of the bilayer resulting in endosome formation were suggested. Initial data suggest a mechanism of antitumor activity of the purified trehalose lipid and its potential for biomedical application.

| S-EPMC7077702 | biostudies-literature

Mining Natural Products with Anticancer Biological Activity through a Systems Biology Approach.

Project description:Natural products, like turmeric, are considered powerful antioxidants which exhibit tumor-inhibiting activity and chemoradioprotective properties. Nowadays, there is a great demand for developing novel, affordable, efficacious, and effective anticancer drugs from natural resources. In the present study, we have employed a stringent in silico methodology to mine and finally propose a number of natural products, retrieved from the biomedical literature. Our main target was the systematic search of anticancer products as anticancer agents compatible to the human organism for future use. In this case and due to the great plethora of such products, we have followed stringent bioinformatics methodologies. Our results taken together suggest that natural products of a great diverse may exert cytotoxic effects in a maximum of the studied cancer cell lines. These natural compounds and active ingredients could possibly be combined to exert potential chemopreventive effects. Furthermore, in order to substantiate our findings and their application potency at a systems biology level, we have developed a representative, user-friendly, publicly accessible biodatabase, NaturaProDB, containing the retrieved natural resources, their active ingredients/fractional mixtures, the types of cancers that they affect, and the corresponding experimentally verified target genes.

| S-EPMC8376429 | biostudies-literature

Dereplication of Natural Products with Antimicrobial and Anticancer Activity from Brazilian Cyanobacteria.

Project description:Cyanobacteria are photosynthetic organisms that produce a large diversity of natural products with interesting bioactivities for biotechnological and pharmaceutical applications. Cyanobacterial extracts exhibit toxicity towards other microorganisms and cancer cells and, therefore, represent a source of potentially novel natural products for drug discovery. We tested 62 cyanobacterial strains isolated from various Brazilian biomes for antileukemic and antimicrobial activities. Extracts from 39 strains induced selective apoptosis in acute myeloid leukemia (AML) cancer cell lines. Five of these extracts also exhibited antifungal and antibacterial activities. Chemical and dereplication analyses revealed the production of nine known natural products. Natural products possibly responsible for the observed bioactivities and five unknown, chemically related chlorinated compounds present only in Brazilian cyanobacteria were illustrated in a molecular network. Our results provide new information on the vast biosynthetic potential of cyanobacteria isolated from Brazilian environments.

| S-EPMC7020483 | biostudies-literature

Anticancer Diiron Vinyliminium Complexes: A Structure-Activity Relationship Study.

Project description:A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R')C(R″)CN(R)(Y)}]CF3SO3 (2-7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69-95% yields from the reactions of diiron μ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R' = R″ = Me) and 3a (R = CH2CH=CH2, Y = R' = Me, R″ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV-Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol-water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2-7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R' = R″ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).

| S-EPMC8398472 | biostudies-literature

Tubulin-interactive natural products as anticancer agents.

Project description:This review provides an overview of the discovery, structures, and biological activities of anticancer natural products that act by inhibiting or promoting the assembly of tubulin to microtubules. The emphasis is on providing recent information on those compounds in clinical use or in advanced clinical trials. The vinca alkaloids, the combretastatins, NPI-2358, the halichondrin B analogue eribulin, dolastatin 10, noscapine, hemiasterlin, and rhizoxin are discussed as tubulin polymerization inhibitors, while the taxanes and the epothilones are the major classes of tubulin polymerization promoters presented, with brief treatments of discodermolide, eleutherobin, and laulimalide. The challenges and future directions of tubulin-interactive natural products-based drug discovery programs are also discussed briefly.

| S-EPMC2765517 | biostudies-other

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