890092-19-0Relevant articles and documents
Novel benzimidazole-acrylonitrile hybrids and their derivatives: Design, synthesis and antimycobacterial activity
Sirim, Mustafa Mert,Krishna, Vagolu Siva,Sriram, Dharmarajan,Unsal Tan, Oya
, (2019/12/30)
This paper reports the synthesis and evaluation of some benzimidazole-acrylonitrile hybrid derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. Among the derivatives studied, 3b was found to be the most active compound with MIC of 0.78 μg/mL against M. tuberculosis. This is a quite good activity compared with ethambutol (MIC = 1.56 μg/mL). Moreover, 3b showed 2.8 log fold reduction in bacterial count of dormant forms of mycobacterium which is more potent than first line drugs isoniazid, ciprofloxacin, rifampicin and moxifloxacin. Having activities against both active and dormant forms of M. tuberculosis, 3b may be a useful candidate for the development of new drugs to treat tuberculosis.
Design and Synthesis of 2-Substitutedphenyl Benzo[D]Thiazole Derivatives and Their β-Amyloid Aggregation and Cholinesterase Inhibitory Activities
Zengin, Merve,Unsal-Tan, Oya,Kü?ükk?l?n?, Tuba Tüylü,Ayazgok, Beyza,Balkan, Ayla
, p. 322 - 328 (2019/07/29)
The occurrence of amyloid-β (Aβ) and reduced cholinergic tranmission are two major hallmarks of Alzheimer’s disease (AD). Therefore, a series of new 2-phenylbenzo[d]thiazoles substituted with azole/piperazine moieties were designed, synthesized, and evaluated as potential dual inhibitors of Aβ aggregation and cholinesterase (ChE) activities. In vitro studies showed that compound 2m containing an imidazole ring strongly inhibited Aβ1–40 (49.2%) and Aβ1-42 aggregation (60.6%). All derivatives exhibited weak inhibitory activities against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Therefore, compound 2m may represent promising therapeutic option for inhibiting Aβ-mediated pathology in AD.
Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK
Bührmann, Mike,Wiedemann, Bianca M.,Müller, Matthias P.,Hardick, Julia,Ecke, Maria,Rauh, Daniel
, (2017/09/23)
In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography.
