Search results for "Structure-Activity Relationship"

Differential specificity of substrate-attached lectins stimulating spreading of GH3-cells under serum-free, hormone-supplemented culture conditions

1982

Most mammalian cells are capable of growth in culture only when they are supplied with an appropriate substrate to which they can adhere and spread. To prepare suitable substrates different lectins were attached onto polystyrene tissue-culture dishes after coating with polylysine. GH3-cells (a pituitary-tumor-cell line) were seeded into the culture dishes containing serum-free, hormone-supplemented medium. When succinylated Concanavalin A (s-Con A), which binds specifically to mannose residues, is attached to the surface an extraordinary spreading of GH3-cells is induced within 15 to 20 min after seeding. Other lectins with a different sugar-binding specificity are less effective in inducin…

Structure-Based Design of an RNA-Bindingp-Terphenylene Scaffold that Inhibits HIV-1 Rev Protein Function

2013

Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance.

2020

Journal of nanobiotechnology 18, 22 (2020). doi:10.1186/s12951-020-0580-1

Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors

2021

Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of action of δ-selective positive allosteric modulator imidazo[1,2-a]pyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chl…

Forchlorfenuron-mimicking haptens: From immunogen design to antibody characterization by hierarchical clustering analysis

2011

To obtain highly-specific and selective forchlorfenuron binders, a collection of functionalized derivatives with different spacer arm locations and lengths was prepared. By immunization with target-mimicking haptens, a large battery of monoclonal and polyclonal antibodies against this synthetic cell regulator was produced and exhaustively characterized in two immunoassay formats using homologous and heterologous conjugates. Antibodies with IC50 values lower than 0.3 nM were successfully raised from the prepared immunogens, thus evidencing the efficacy of the explored strategies. In order to identify significant epitopes in the antibody-antigen interaction, a series of new chemical forchlorf…

Histidine residues near the N terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation.

1994

Chemical modification of histidine residues in staphylococcal alpha-toxin leads to loss of functional activity. Site-directed mutants of the toxin in which each of the four histidine residues was replaced by several amino acids were therefore produced. The mutant proteins were purified and characterized. Exchange of H-259 or H-144 was sometimes tolerated without reduction in hemolytic activity. These histidine residues are thus not essential for toxin function. Exchange of H-35 and H-48, however, had marked effects. H-35 mutant toxins bound with high affinity to rabbit erythrocytes but displayed faulty oligomerization and were unable to form pores. H-48 mutant toxins also had severely impai…

Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides

2007

Abstract A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concent…

Synthesis and antiproliferative activity of triazenoindazoles and triazenopyrazoles: a comparative study.

2003

Several triazenoindazoles and triazenopyrazoles were prepared transforming the appropriate aminoindazoles and aminopyrazoles in the corresponding diazonium salts which were reacted with dimethylamine, diethylamine and pyrrolidine. All the triazenes were tested for their antiproliferative activity against K562, HL60, L1210 and MCF7 cell lines. The biological data showed that the benzocondensation plays a positive role on the antiproliferative activity. The (1)H-NMR spectra showed that the rotational barrier around the N(2)-N(3) bond in the triazene group can be influenced both by the position of this group in the indazole nucleus and by the substitution pattern in the benzene moiety.

Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors.

2012

Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure.

Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and…

2009

In the context of the design and synthesis of DNA ligands, some new hetarene annelated carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds was examined by the NCI antitumor screening. Furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA-binding properties and inhibition of DNA related functional enzymes of this new…