53923-99-2Relevant articles and documents
Design and synthesis of new pyrazolylbenzimidazoles as sphingosine kinase-1 inhibitors
Galal, Shadia A.,Omar, Mohamed A.,Khairat, Sarah H. M.,Ragab, Fatma A. F.,Roy, Sonam,Naqvi, Ahmad Abu Turab,Hassan, Md. Imtaiyaz,El Diwani, Hoda I.
, p. 1614 - 1634 (2021)
Sphingosine-1 kinase (SphK1) is one of the important enzymes of phospholipids and its inhibition is one of the therapeutic strategies for different diseases. SphK1 over expression is observed in different types of cancer indicating its important role in tumor growth. In search of effective SphK1 inhibitors, a new series of pyrazolylbenzimidazoles was synthesized and evaluated as sphingosine kinase-1 (SphK1) inhibitors. In order to evaluate the binding affinities of all the synthesized compounds, all compounds were subjected to docking analysis and fluorescence quenching. The results indicated that there is a consistency between the docking and the fluorescence quenching results, which revealed that compounds 47 and 48 exhibited significant decrease in the fluorescence intensity of SphK1 as well as they formed stable protein–ligand complexes. In addition, enzyme inhibition assay was performed which showed effective inhibitory potential toward SphK1. Moreover, IC50 values displayed that compounds 47 and 48 were the most promising compounds. In addition, antiproliferation study for all the synthesized compounds was performed against NCI-60 cell line panel. The target compounds 47 and 48 demonstrated effective antitumor activity and growth inhibitory potential toward cancer cell lines. Most of these compounds fit well into the ATP-binding site of SphK1 and form significant hydrogen-bonding interactions with catalytically relevant residues as predicted by molecular docking. In this article, insight has been given for the importance of pyrazolylbenzimidazoles as SphK1 inhibitors and the perspectives that they hold for future research. [Figure not available: see fulltext.]
Design, synthesis and in-silico & in vitro enzymatic inhibition assays of pyrazole-chalcone derivatives as dual inhibitors of α-amylase & DPP-4 enzyme
Nidhar, Manisha,Sonker, Priyanka,Sharma, Vishal Prasad,Kumar, Sanjay,Tewari, Ashish Kumar
, p. 1707 - 1720 (2022/02/07)
A series of pyrazole-chalcone derivatives were designed, synthesized and evaluated for their in vitro α-amylase & DPP-4 inhibitory activity. The structure of the compounds thus prepared was confirmed by analytical, and spectral techniques, 1H-NMR, 13C-NMR and Mass spectroscopy. To preliminarily investigate the molecular targets and to confirm the experimental activity testing for these anti-diabetic compounds, the molecular docking studies were determined, using different target receptors i.e., DPP-4 (PDB: 2OLE), PPARγ (PDB: 5Y2O) & α-amylase enzyme (PDB: 5E0F). The docking study results revealed that pyrazole-chalcone derivatives exhibited better binding interaction to α-amylase enzyme over the DPP-4 enzyme & PPARγ. Depending on in silico experiments the designed compounds were selectively prioritized for synthesis. The synthesized compounds were subjected to enzyme-based in vitro α-amylase, DPP-4 inhibitory, and antioxidant activity. ADMET parameters like HBD, HBA, PSA, cLogP, molecular weight, bioavailability, and drug-likeness further confirmed that the compounds are potential lead compounds for future study. Compounds 4d and 6a exhibited highest activity toward α-amylase enzyme and DPP-4 enzyme.
