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).
Tasisulam (LY573636) is a SPLAM (SPLicing inhibitor sulfonAMide) th at bridges RNA binding motif protein 39 (RBM39; CAPERα, HCC1) and DCAF15 for interaction, thereby 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.
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.
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