56934-06-6Relevant articles and documents
A Structure-Activity Relationship Study of Bitopic N 6-Substituted Adenosine Derivatives as Biased Adenosine A1 Receptor Agonists
Aurelio, Luigi,Baltos, Jo-Anne,Ford, Leigh,Nguyen, Anh T. N.,J?rg, Manuela,Devine, Shane M.,Valant, Celine,White, Paul J.,Christopoulos, Arthur,May, Lauren T.,Scammells, Peter J.
, p. 2087 - 2103 (2018)
The adenosine A1 receptor (A1AR) is a potential novel therapeutic target for myocardial ischemia-reperfusion injury. However, to date, clinical translation of prototypical A1AR agonists has been hindered due to dose limiting adverse effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting of an adenosine pharmacophore linked to an allosteric moiety, could stimulate cardioprotective A1AR signaling in the absence of unwanted bradycardia. Therefore, this study aimed to investigate the structure-activity relationship of compound 1 biased agonism. A series of novel derivatives of 1 were synthesized and pharmacologically profiled. Modifications were made to the orthosteric adenosine pharmacophore, linker, and allosteric 2-amino-3-benzoylthiophene pharmacophore to probe the structure-activity relationships, particularly in terms of biased signaling, as well as A1AR activity and subtype selectivity. Collectively, our findings demonstrate that the allosteric moiety, particularly the 4-(trifluoromethyl)phenyl substituent of the thiophene scaffold, is important in conferring bitopic ligand bias at the A1AR.
Synthesis and pharmacological evaluation of modified adenosines joined to mono-functional platinum moieties
D'Errico, Stefano,Oliviero, Giorgia,Borbone, Nicola,Piccialli, Vincenzo,Pinto, Brunella,De Falco, Francesca,Maiuri, Maria Chiara,Carnuccio, Rosa,Costantino, Valeria,Nici, Fabrizia,Piccialli, Gennaro
, p. 9339 - 9353 (2014)
The synthesis of four novel platinum complexes, bearing N6-(6- Aminohexyl) adenosine or a 1,6-di(adenosin-N6-yl)-hexane respectively, as ligands of monofunctional cisplatin or monochloro(ethylendiamine)platinum(II), is reported. The chemistry exploits the high affinity of the charged platinum centres towards the N7 position of the adenosine base system and a primary amine of an alkyl chain installed on the C6 position of the purine. The cytotoxic behaviour of the synthesized complexes has been studied in A549 adenocarcinomic human alveolar basal epithelial and MCF7 human breast adenocarcinomic cancer cell lines, in order to investigate their effects on cell viability and proliferation.
Fluorescence-Lifetime-Sensitive Probes for Monitoring ATP Cleavage
Hammler, Daniel,Marx, Andreas,Zumbusch, Andreas
supporting information, p. 15329 - 15335 (2018/09/25)
Adenosine triphosphate (ATP) probes modified with fluorescence dyes that change their fluorescence properties upon cleavage are an interesting tool for monitoring enzymatic ATP turnover. As a readout parameter, fluorescence lifetime is attractive because it is nearly independent of concentration. In our study, we synthesised and investigated fifteen different ATP analogues, in which the fluorophores were attached to the γ-phosphate of ATP. All analogues showed distinctly different fluorescence lifetimes compared to the corresponding values of the free fluorophores. Both increases and decreases in fluorescence lifetime were observed upon attachment to ATP. To shed light on the photophysical processes governing the lifetime changes, we performed photoelectron spectroscopy in air (PESA) to determine HOMO energy levels and time-resolved fluorescence spectroscopy to obtain rate constants. We present evidence that fluorescence quenching in the compounds tested is dynamic and attributed to photoinduced electron transfer (PET), whereas fluorescence lifetime increases are caused by stacking interactions between chromophore and the nucleobase reducing non-radiative relaxation. Finally, we demonstrate that enzymatic cleavage of the ATP analogues presented can be followed by continuous monitoring of fluorescence lifetime changes.
New conjugates of mycophenolic acid and their antiproliferative activity
Prejs, Micha?,Cholewinski, Grzegorz,Siebert, Agnieszka,Trzonkowski, Piotr,Dzierzbicka, Krystyna
, p. 1057 - 1062 (2016/09/28)
The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N6-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a–h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity. The compound 4b possessing 1,3-diamine spacer exhibited the most promising results and can be considered to further investigations.
