25314-95-8Relevant academic research and scientific papers
Thiosemicarbazide binds with the dicopper center in the competitive inhibition of mushroom tyrosinase enzyme: Synthesis and molecular modeling of theophylline analogues
Bari, Ahmed,Ghani, Usman,Ali Syed, Saeed,Riazullah
, (2021/02/09)
Theophylline is long known for its anti-ageing and anti-oxidative properties. Moreover, Tyrosinase is a crucial enzyme that regulates the melanin synthetic pathway, which is involved in various physiological metabolic processes including aging. The current paper describes the synthesis of various heterocyclic systems coupled with theophylline moiety along with their tyrosinase inhibition activity in view to identify the potent nucleus. Around 19 compounds were synthesized and screened for enzyme inhibition. Based on the current study, it is suggested that compound 18 having thiosemicarbazide has strong enzyme inhibition potential. The enzyme kinetics and docking studies provide important insights into how the compound interacts with the mushroom tyrosinase active site. The work will provide clue to developing new, potent tyrosinase inhibitors for drug development.
MLKL INHIBITORS
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Paragraph 0447-0448; 0454-0455; 0465-0466; 0801-0802, (2018/09/26)
Purine derivatives that inhibit cellular necroptosis and/or human MLKL, pharmaceutical compositions thereof, and methods of treating an MLKL-mediated disorder with an effective amount of the compound or composition. Said MLKL-mediated disorder is pathology associated necroptosis, including ischemia-reperfusion damage, neurodegeneration, and inflammatory diseases such as acute pancreatitis, multiple sclerosis, inflammatory bowel disease, and allergic colitis.
Discovery of a new class of highly potent necroptosis inhibitors targeting the mixed lineage kinase domain-like protein
Yan, Bo,Liu, Lei,Huang, Shaoqiang,Ren, Yan,Wang, Huayi,Yao, Zhenglin,Li, Lin,Chen, She,Wang, Xiaodong,Zhang, Zhiyuan
supporting information, p. 3637 - 3640 (2017/04/03)
We report the development of novel Mixed Lineage Kinase Domain-Like protein (MLKL) inhibitors with single nanomolar potency (compound 15 is also named as TC13172). Using the converting biochemistry to chemistry activity-based protein profiling (BTC-ABPP) method, we were able to determine that the inhibitors covalently bind to Cysteine86 (Cys-86) of MLKL. This is the first example of the use of LC-MS/MS to identify the binding site of an MLKL inhibitor. The novel MLKL inhibitors provide powerful tools to study the biological function of MLKL and demonstrate that MLKL should be viewed as a druggable target.
Synthesis and Properties of 8-Nitro-7-Alkylated Theophylline Derivatives
Mosselhi, Mosselhi A. N.,Abbass, Ikhlass M.
, p. 179 - 186 (2007/10/02)
8-Nitrotheophylline (3) was alkylated with alkylhalides to obtain the corresponding 8-nitro-7-alkylated theophylline derivatives (4a-d).The reduction of 4a-d provided 8-aminoderivatives (5a-d).Heating 4a-d in the concentrated HCl gave the corresponding 8-chloroderivatives (6a-d).The products 5a and 5b reacted with 4-acetamidobenzenesulphonyl chloride to provide 8-(4'-acetamidobenzenesulphonamido)theophyllines (7a) and (7b).The acid hydrolysis of 7a and 7b gave the corresponding 8-(4'-aminobenzenesulphonamido)theophyllines (8a) and (8b), which were also products of the reaction of 6b and 6c with 4-acetamidobenzenesulphonamide, followed by the acid hydrolysis.The reaction of 6a and 6b with benzylamine in dimethylformamide resulted unexpectedly in the 8-dimethylaminoderivatives (9a) and (9b), respectively. Key words: 8-nitrotheophylline, alkylhalides, HCl, acid hydrolysis.
