51769-38-1Relevant articles and documents
Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2
Nguyen, William,Lee, Erinna F.,Evangelista, Marco,Lee, Mihwa,Harris, Tiffany J.,Colman, Peter M.,Smith, Nicholas A.,Williams, Luke B.,Jarman, Kate E.,Lowes, Kym N.,Haeberli, Cécile,Keiser, Jennifer,Smith, Brian J.,Fairlie, W. Douglas,Sleebs, Brad E.
, p. 1143 - 1163 (2021/02/22)
Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm. The B cell lymphoma-2 (BCL-2)-regulated apoptotic cell death pathway in schistosomes was recently characterized and shown to share similarities with the intrinsic apoptosis pathway in humans. Here, we exploit structural differences in the human and schistosome BCL-2 (sBCL-2) pro-survival proteins toward a novel treatment strategy for schistosomiasis. The benzothiazole hydrazone scaffold previously employed to target human BCL-XL was repurposed as a starting point to target sBCL-2. We utilized X-ray structural data to inform optimization and then applied a scaffold-hop strategy to identify the 5-carboxamide thiazole hydrazone scaffold (43) with potent sBCL-2 activity (IC50 30 nM). Human BCL-XL potency (IC50 13 nM) was inadvertently preserved during the optimization process. The lead analogues from this study exhibit on-target activity in model fibroblast cell lines dependent on either sBCL-2 or human BCL-XL for survival. Further optimization of the thiazole hydrazone class is required to exhibit activity in schistosomes and enhance the potential of this strategy for treating schistosomiasis.
Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists
Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Javed, Kalim,Bano, Sameena,Ali, Yakub,Dhulap, Abhijeet,Alam, Perwez,Pasha, M. A. Qadar
, p. 354 - 362 (2016/10/19)
Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.
Synthesis and antibacterial evaluation of a novel series of 2-(1,2-dihydro-3-oxo-3H-pyrazol-2-yl)benzothiazoles
Stella, Alessandro,Segers, Kenneth,De Jonghe, Steven,Vanderhoydonck, Bart,Rozenski, Jef,Anne, Jozef,Herdewijn, Piet
experimental part, p. 253 - 265 (2011/09/30)
The 2-(1,2-dihydro-3-oxo-3H-pyrazol-2-yl)benzothiazole scaffold was selected as a central core structure for the discovery of novel antibacterial compounds. A systematic variation of the substituents on the oxo-pyrazole moiety, as well as on the benzo moiety, led to the creation of a small and focused library of benzothiazoles that was subjected to antibacterial screening. In a first round of screening, activity of the compounds against six representative microorganisms was established. For the most potent congeners, MIC values against S. aureus and P. aeruginosa were determined. The structure-activity relationship study clearly revealed that subtle structural variations influence the antibacterial activity to a large extent. The most potent congeners displayed MIC values of 3.30 μM.