81514-10-5Relevant articles and documents
Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma
Ali, Wesam,Battistelli, Cecilia,D?browska, Monika,Handzlik, Jadwiga,Honkisz-Orzechowska, Ewelina,Jacob, Claus,Kincses, Annamária,Latacz, Gniewomir,Nové, Márta,Rasile, Manuela Monica,Romanelli, Annalisa,Spengler, Gabriella,Starek, Ma?gorzata,Szymańska, Ewa,Zwergel, Clemens
supporting information, (2020/06/05)
Multidrug resistance (MDR) in cancer cells is a crucial aspect to consider for a successful cancer therapy. P-gp/ABCB1, a member of ABC transporters, is involved in the main tumour MDR mechanism, responsible for the efflux of drugs and cytotoxic substances. Herein, we describe a discovery of potent selenium-containing ABCB1 MDR efflux pump modulators with promising anticancer activity. On three groups of selenoethers comprehensive studies in terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5–7) were significantly more effective than the reference inhibitor verapamil (up to 2.6-fold at a 10-fold lower concentration) modulating ABCB1-efflux pump, also possessing a good drug-drug interaction profile. The best compound (6) was further evaluated in human JURKAT T-lymphocytic cancer cells for its impact on cell proliferation rate. Mechanistically, the expression of cyclin D1, an enhancer of the cell cycle, decreases, while p53, an inhibitor of cell proliferation, was up-regulated upon the treatment with compound 6 alone or in combination with the chemotherapeutic agent doxorubicin. In summary, a new chemical space of highly active selenium-containing anticancer agents has been discovered, with a new lead compound 6 that warrants more in-depth biological evaluation and further pharmacomodulation.
Synthesis and in vitro evaluation of novel indole-based sigma receptors ligands
Yarim, Mine,Koksal, Meric,Schepmann, Dirk,Wuensch, Bernard
experimental part, p. 869 - 875 (2012/07/03)
To investigate the molecular features involved in sigma (σ) receptors binding, a series of compounds based on indole scaffolds were synthesized and their chemical structures were confirmed by 1H-NMR, IR, and elemental analysis. Their affinity t
Synthesis of new 1,2,3-benzotriazin-4-one-arylpiperazine derivatives as 5-HT(1A) serotonin receptor ligands
Caliendo, Giuseppe,Fiorino, Ferdinando,Grieco, Paolo,Perissutti, Elisa,Santagada, Vincenzo,Severino, Beatrice,Bruni, Giancarlo,Romeo, Maria Rosaria
, p. 533 - 538 (2007/10/03)
A series of novel 1,2,3-benzotriazin-4-one derivatives was prepared and evaluated as ligands for 5-HT receptors. Radioligand binding assays proved that the majority of the novel compounds behaved as good to excellent ligands at the 5-HT(1A) receptor, some of which were selective with respect 5-HT(2A) and 5-HT(2C) receptors. Six analogues (1a, 2a, 2b, 2c, 2e and 2i) were selected and further evaluated for their binding affinities on D1, D2 dopaminergic and α1-, α2-adrenergic receptors. A o-OCH3 derivative (2e) bound at 5-HT(1A) sites with subnanomolar affinity (IC50=0.059 nM) and shows high selectivity over all considered receptors and may offer a new lead for the development of therapeutically efficacious agents. Copyright (C) 2000 Elsevier Science Ltd.
