13338-00-6Relevant articles and documents
Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity
Bozdag, Murat,Alafeefy, Ahmed Mahmoud,Altamimi, Abdul Malik,Vullo, Daniela,Carta, Fabrizio,Supuran, Claudiu T.
, p. 677 - 683 (2017)
Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a–f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a–c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7?nM.
Discovery of Halogenated Benzothiadiazine Derivatives with Anticancer Activity**
Huwaimel, Bader I.,Bhakta, Myla,Kulkarni, Chaitanya A.,Milliken, Alexander S.,Wang, Feifei,Peng, Aimin,Brookes, Paul S.,Trippier, Paul C.
, p. 1143 - 1162 (2021/02/01)
Mitochondrial respiratory complex II (CII), also known as succinate dehydrogenase, plays a critical role in mitochondrial metabolism. Known but low potency CII inhibitors are selectively cytotoxic to cancer cells including the benzothiadiazine-based anti-hypoglycemic diazoxide. Herein, we study the structure-activity relationship of benzothiadiazine derivatives for CII inhibition and their effect on cancer cells for the first time. A 15-fold increase in CII inhibition was achieved over diazoxide, albeit with micromolar IC50 values. Cytotoxicity evaluation of the novel derivatives resulted in the identification of compounds with much greater antineoplastic effect than diazoxide, the most potent of which possesses an IC50 of 2.93±0.07 μM in a cellular model of triple-negative breast cancer, with high selectivity over nonmalignant cells and more than double the potency of the clinical agent 5-fluorouracil. No correlation between cytotoxicity and CII inhibition was found, thus indicating an as-yet-undefined mechanism of action of this scaffold. The derivatives described herein represent valuable hit compounds for therapeutic discovery in triple-negative breast cancer.
"a Sweet Combination": Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII
Bua, Silvia,Lomelino, Carrie,Murray, Akilah B.,Osman, Sameh M.,Alothman, Zeid A.,Bozdag, Murat,Abdel-Aziz, Hatem A.,Eldehna, Wagdy M.,McKenna, Robert,Nocentini, Alessio,Supuran, Claudiu T.
, p. 321 - 333 (2020/01/02)
The sweeteners saccharin (SAC) and acesulfame K (ACE) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design s
