Uses
The sodium salt of Tasisulam has potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS).
Biological Activity
Tasisulam (LY573636) is a SPLAM (SPLicing inhibitor sulfonAMide) th at bridges RNA binding motif protein 39 (RBM39; CAPERαHCC1) and DCAF15 for interactionthereby promoting (CUL4-DDB1-DDA1-DCAF15) E3 ubiquitin ligase complex-mediated RBM39 ubiquitination and subsequent proteasomal degradation. Tasisulam exerts selective toxicity in parental HCT116 cancer cultures (IC50 = 6.5 μM)but not those harboring non-CUL4-DCAF15-associating RBM39 G268V mutant even at a high concentration of 50 μM.
Synthesis
General procedure for the synthesis of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide from 2,4-dichlorobenzoic acid and the compound (CAS:1152981-12-8): 0.5 mmol (0.0955 g) of 2,4-dichlorobenzoic acid, 0.75 mmol (0.2011 g) of 2-bromothiophene-sulfonamide azide, and 0.025 mmol (0.0086 g) octacarbonyldicobalt in a 25 mL reaction tube; subsequently, 4 mL of acetonitrile solvent was added via a microsyringe, and the reaction system was stirred at 80 °C for 4 hours. Upon completion of the reaction, the mixture was concentrated by rotary evaporation and purified by column chromatography (column conditions: 200-300 mesh silica gel, mobile phase ethyl acetate:petroleum ether=1:4) to give 0.1583 g of the target product as a white solid in 76% yield.
References
[1] Chemistry--A European Journal, 2012, vol. 18, # 45, p. 14444 - 14453,10
[2] Chemistry - A European Journal, 2012, vol. 18, # 45, p. 14444 - 14453
[3] Journal of Organic Chemistry, 2018, vol. 83, # 16, p. 9364 - 9369
[4] Patent: CN108558822, 2018, A. Location in patent: Paragraph 0035; 0036; 0037; 0040; 0043
