476278-47-4Relevant academic research and scientific papers
6-Benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17-HSD10 and potential drugs for Alzheimer's disease treatment: Design, synthesis and in vitro evaluation
Benek, Ondrej,Hroch, Lukas,Aitken, Laura,Dolezal, Rafael,Hughes, Rebecca,Guest, Patrick,Benkova, Marketa,Soukup, Ondrej,Musil, Karel,Kuca, Kamil,Smith, Terry K.,Gunn-Moore, Frank,Musilek, Kamil
, p. 345 - 358 (2017/06/20)
Background: The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17-hydroxysteroid dehydrogenase type 10 (17-HSD10) has been connected with the pathogenesis of Alzheimer's disease (AD). ABAD/17-HSD10 is a binding site for the amyloid-beta peptide (A) inside the mitochondrial matrix where it exacerbates A toxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Methods: As ABAD’s enzymatic activity is required for mediating A toxicity, its inhibition presents a promising strategy for AD treatment. In this study, a series of new benzothiazolylurea analogues have been prepared and evaluated in vitro for their potency to inhibit ABAD/17-HSD10 enzymatic activity. The most potent compounds have also been tested for their cytotoxic properties and their ability to permeate through blood-brain barrier has been predicted. To explain the structure-activity relationship QSAR and pharmacophore studies have been performed. Results and Conclusion: Compound 12 was identified being the most promising hit compound with good inhibitory activity (IC50 = 3.06 ± 0.40 M) and acceptable cytotoxicity profile comparable to the parent compound of frentizole. The satisfactory physical-chemical properties suggesting its capability to permeate through BBB make compound 12 a novel lead structure for further development and biological assessment.
Synthesis of benzothiazole derivatives and their biological evaluation as anticancer agents
Caputo, Rosanna,Calabro, Maria Luisa,Micale, Nicola,Schimmer, Aaron D.,Ali, Moshin,Zappala, Maria,Grasso, Silvana
, p. 2644 - 2651 (2012/11/07)
This article describes the synthesis and the biological evaluation of two sets of benzothiazole derivatives bearing at C-2 an arylamide (1a-e, 2a-e) or an arylurea (3a-d, 4a-d) moiety. Five compounds (3d and 4a-d) were selected and screened by the National Cancer Institute for the in vitro primary anticancer assay against a panel of 60 human tumor cell lines. Compounds 4a and 4c showed interesting anticancer activities, more marked for compound 4c. All compounds were also submitted to a preliminary in vitro assay as potential inhibitors of the ubiquitin-activating enzyme (E1), but they lacked significant activity. Springer Science+Business Media, LLC 2011.
