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 first pentafluorosulfanyl analogs of mefloquine.

ABSTRACT: Two novel SF5 analogs of the antimalarial agent mefloquine were synthesized in 5 steps and 10-23% overall yields and found to have improved activity and selectivity against malaria parasites. This work also represents the first report of SF5-substituted quinolines.

SUBMITTER: Wipf P

PROVIDER: S-EPMC2929370 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and biological evaluation of the first pentafluorosulfanyl analogs of mefloquine.

Wipf Peter P Mo Tingting T Geib Steven J SJ Caridha Diana D Dow Geoffrey S GS Gerena Lucia L Roncal Norma N Milner Erin E EE

Organic & biomolecular chemistry 20090807 20

Two novel SF5 analogs of the antimalarial agent mefloquine were synthesized in 5 steps and 10-23% overall yields and found to have improved activity and selectivity against malaria parasites. This work also represents the first report of SF5-substituted quinolines. ...[more]

PMID: 19795052

Similar Datasets

Pentafluorosulfanyl-containing flufenamic acid analogs: Syntheses, properties and biological activities.

Project description:Pentafluorosulfanyl-containing analogs of flufenamic acid have been synthesized in high yields. Computationally, pKa, LogP and LogD values have been determined. Initial bioactivity studies reveal effects as ion channel modulators and inhibitory activities on aldo-keto reductase 1C3 (AKR1C3) as well as COX-1 and COX-2.

| S-EPMC4599580 | biostudies-literature

Synthesis and biological evaluation of neopeltolide and analogs.

Project description:The synthesis of neopeltolide analogues that contain variations in the oxazole-containing side chain and in the macrolide core are reported along with the GI(50) values for these compounds against MCF-7, HCT-116, and p53 knockout HCT-116 cell lines. Although biological activity is sensitive to changes in the macrocycle and the side chain, several analogues displayed GI(50) values of <25 nM. Neopeltolide and several of the more potent analogues were significantly less potent against p53 knockout cells, suggesting that p53 plays an auxiliary role in the activity of these compounds.

| S-EPMC3308185 | biostudies-literature

Synthesis and biological evaluation of semi-synthetic albocycline analogs.

Project description:Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 μg/mL). Described herein is the synthesis and evaluation of a novel series analogs derived from albocycline by functionalization at three specific sites: the C2-C3 enone, the tertiary carbinol at C4, and the allylic C16 methyl group. Exploration of the structure-activity relationships (SAR) by means of minimum inhibitory concentration assays (MICs) revealed that C4 ester analog 6 was twice as potent as ALB, which represents a class of lead compound that can be further studied to address multi-drug resistant pathogens.

| S-EPMC7577960 | biostudies-literature

Synthesis and Biological Evaluation of Subglutinol Analogs for Immunomodulatory Agents.

Project description:Autoimmune diseases are chronic inflammatory diseases associated with high morbidity and mortality. Treatment options for autoimmune diseases have increased over the past several decades, but they are, in general, limited in their clinical efficacy due to high toxicity and lack of selectivity. Thus, efforts must be made to identify new immunomodulatory agents that are effective through a novel mechanism to circumvent existing side effects. To define the structural requirements of subglutinols for immunomodulatory activity and to provide guiding principles on future therapeutic development, we prepared and evaluated several subglutinol analogs for their immunomodulatory activities. Our efforts identified a subglutinol analog with reduced structural complexity as a potential lead compound for future autoimmune drug development. Our study will provide an important framework for the design of potent and nontoxic immunomodulating agents derived from subglutinols.

| S-EPMC7367062 | biostudies-literature

SYNTHESIS AND BIOLOGICAL EVALUATION OF BIARYL ANALOGS OF ANTITUBULIN COMPOUNDS.

Project description:This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [(3)H] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site.

| S-EPMC3472429 | biostudies-literature

Novel Carbonyl Analogs of Tamoxifen: Design, Synthesis, and Biological Evaluation.

Project description:Aim of this work was to provide tamoxifen analogs with enhanced estrogen receptor (ER) binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known ER inhibitor ICI182,780. Theoretical calculations and molecular modeling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

| S-EPMC5622936 | biostudies-literature

Synthesis and biological evaluation of largazole zinc-binding group analogs.

Project description:Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed in a variety of different diseases, leading to a recent focus of HDACs as attractive drug targets. The natural product largazole is one of the most potent natural HDAC inhibitors discovered so far and a number of largazole analogs have been prepared to define structural requirements for its HDAC inhibitory activity. However, previous structure-activity relationship studies have heavily investigated the macrocycle region of largazole, while there have been only limited efforts to probe the effect of various zinc-binding groups (ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of the analogs tested were as potent or selective as largazole, the Zn2+-binding affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect that our findings will aid in building a deeper understanding of the role of ZBGs in HDAC inhibition as well as provide an important basis for the future development of new largazole analogs with non-thiol ZBGs as novel therapeutics for cancer.

| S-EPMC5494147 | biostudies-literature

Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation.

Project description:Microtubules, composed of ?/? tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling.

| S-EPMC3179862 | biostudies-literature

Semisynthetic Analogs of the Antibiotic Fidaxomicin-Design, Synthesis, and Biological Evaluation.

Project description:The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Among the main limitations for this compound, its low water solubility impacts further clinical uses. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free preparative approach from the natural product. An increase in solubility of up to 25-fold with largely retained activity was observed. Furthermore, hybrid antibiotics were prepared that show improved antibiotic activities.

| S-EPMC7734799 | biostudies-literature

Synthesis and biological evaluation of solithromycin analogs against multidrug resistant pathogens.

Project description:Novel antibacterial drugs that treat multidrug resistant pathogens are in high demand. We have synthesized analogs of solithromycin using Cu(I)-mediated click chemistry. Evaluation of the analogs using Minimum Inhibitory Concentration (MIC) assays against resistant Staphylococcus aureus, Escherichia coli, and multidrug resistant pathogens Enterococcus faecium and Acinetobacter baumannii showed they possess potencies similar to those of solithromycin, thus demonstrating their potential as future therapeutics to combat the existential threat of multidrug resistant pathogens.

| S-EPMC6487207 | 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