2.B.85. The Synthetic Sulfonamide NH-containing Compound Ion Transporter (SSNH-IT) Family
Shinde and Talukdar 2018 synthesized HCl cotransporters containing an acidic sulfonamide NH group (compounds 30a–30g shown in the figure below. A variety of assays including pH dissipation assays using HPTS encapsulated within vesicles were used to elucidate the transport mechanism facilitated by these systems (Davis et al. 2020). These compounds function by transporting chloride across a lipid bilayer and then decomplex and deprotonate, allowing the anionic form of the deprotonated sulfonamide to diffuse back across the membrane to bind another equivalent of HCl. The anion transport activity of the series was found to be 30d > 30b > 30e > 30f > 30c > 30a > 30g (see below).
As noted above, Shinde and Talukdar 2019 have reported the sulfonamide-based chloride receptor 19 (see figure below) The sulfonamide-NH receptors 19 can be deprotonated under physiological conditions as their pKa ranges from 7.28 to 7.44. The molecule 19b with a CH3 substitutent on the aromatic ring has an EC50 value of 2.33 μM and operates via a H+/Cl− symport mechanism. The ability of the transporters to accomplish intracellular acidification has been applied to cancer therapy.