Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters

Database
Language
Affiliation country
Publication year range
1.
Chemistry ; 26(24): 5419-5433, 2020 Apr 24.
Article in English | MEDLINE | ID: mdl-31958176

ABSTRACT

A series of 16 dinuclear thiopyridone-based organometallics with excellent water solubility, increased stability and remarkable cytotoxicity were synthesized and characterized. The complexes of this work formed dimeric species featuring a double positive charge in polar protic solvents, accounting for their outstanding solubility in aqueous solution. Most of them displayed higher antiproliferative activity than their parental thiomaltol complex, with unexpected cytotoxicity trends depending on the employed metal center, ligand modification, and cell line. Insights into their behavior in biological systems were gathered by means of amino-acid interaction studies, cytotoxicity tests in 3D spheroid models, laser ablation, cellular accumulation measurements, as well as cell cycle experiments.


Subject(s)
Coordination Complexes/chemical synthesis , Pyrans/chemical synthesis , Thiones/chemical synthesis , Cell Cycle , Cell Line, Tumor , Coordination Complexes/chemistry , Gene Library , Humans , Ligands , Pyrans/chemistry , Solubility , Thiones/chemistry
2.
Molecules ; 23(4)2018 Mar 24.
Article in English | MEDLINE | ID: mdl-29587344

ABSTRACT

Efficient optimization procedures in chiral catalysis are usually linked to a straightforward strategy to access groups of structurally similar catalysts required for fine-tuning. The ease of building up such ligand libraries can be increased when the structure-modifying step (introduction of a substituent) is done at a later stage of the synthesis. This is demonstrated for the extended family of di- and tetranaphtho azepinium compounds, widely used as chiral phase transfer catalysts (PTC). Using 2,6-diiodo-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine and 4,8-diiodo-6,7-dihydro-5H-dibenzo[c,e]azepine, respectively, as key intermediates, 18 spiro-azepinium compounds were synthesized in a total yield of 25-42% over 6-7 steps from 1,1'-binaphthyl-2,2'-dicarboxylic acid or diphenic acid, respectively. The replacement of iodo groups with aryl substituents was performed as the last or the penultimate step of the synthesis.


Subject(s)
Azepines/chemistry , Spiro Compounds/chemical synthesis , Catalysis , Crystallography, X-Ray , Ligands , Models, Molecular , Molecular Structure , Spiro Compounds/chemistry , Stereoisomerism
3.
Chemistry ; 23(62): 15655-15665, 2017 Nov 07.
Article in English | MEDLINE | ID: mdl-28703941

ABSTRACT

The ongoing search for bioactive natural products has led to the development of new genome-based screening approaches to identify possible phosphonate producing microorganisms. From the identified phosphonate producers, several until now unknown phosphonic acid natural products were isolated, including (hydroxy)nitrilaphos (4 and 5) and (hydroxy)phosphonocystoximate (7 and 6). We present the synthesis of phosphonocystoximate via an aldoxime intermediate. Chlorination and coupling with methyl N-acetylcysteinate furnished 6 after global deprotection. The obtained experimental data confirm the previously assigned structure of the natural product. We were also able to determine the absolute configuration of (-)-hydroxynitrilaphos. Chiral resolution of diethyl cyanohydroxymethylphosphonate (24) with Noe's lactol furnished both enantiomers of 4. Conversion of (+)-24 to (R)-2-amino-1-hydroxyethylphosphonic acid by reduction of the cyano-group showed (-)-hydroxynitrilaphos ultimately to be S-configured. Further, we present a 13 C-isotope labeling strategy for 4 and 5 that will possibly solve the question of whether hydroxynitrilaphos is a biosynthetic intermediate or a downstream product of hydroxyphosphonocystoximate biosynthesis.


Subject(s)
Biological Products/metabolism , Nitriles/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , Carbon Isotopes/chemistry , Isotope Labeling , Magnetic Resonance Spectroscopy , Molecular Conformation , Nitriles/chemical synthesis , Phosphorous Acids/chemistry , Spectrometry, Mass, Electrospray Ionization , Stereoisomerism
4.
Pharmaceutics ; 15(11)2023 Nov 15.
Article in English | MEDLINE | ID: mdl-38004604

ABSTRACT

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy. The synthesis of [103Ru]BOLD-100, radiolabeled with carrier added (c.a.) ruthenium-103, was established and the product was characterized by HPLC and UV/Vis spectroscopy. In order to compare the radiolabeled and non-radioactive versions of BOLD-100, both complexes were fully evaluated in vitro and in vivo. The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [103Ru]BOLD-100.

5.
Nucl Med Biol ; 70: 46-52, 2019 03.
Article in English | MEDLINE | ID: mdl-30831342

ABSTRACT

The combination of low molecular weight, reversible human serum albumin (HSA) binders with targeted radiopharmaceuticals in dual-targeted radioconjugates holds great promise, in particular for endoradiotherapy. Attachment of HSA-binders to radiopharmaceuticals extends their blood circulation time and results in an enhanced tumour uptake as well as often in an improved pharmacokinetic profile. In this mini-review, an overview of currently pursued approaches of this novel strategy is provided.


Subject(s)
Radiopharmaceuticals/chemistry , Serum Albumin, Human/chemistry , Humans , Molecular Weight
SELECTION OF CITATIONS
SEARCH DETAIL