Ischemia reperfusion injury is responsible for impaired graft functioning in organ transplants,
cerebral dysfunction, ischemic heart diseases, systemic inflammatory response syndrome,
gastrointestinal dysfunction, and multiple organ dysfunction syndromes. Intracellular pH is critical
for cell survival in ischemia reperfusion injury. Sodium hydrogen exchanger I and carbonic anhydrase
II are critical in the regulation of intracellular pH. Inhibition of sodium hydrogen exchanger I
and carbonic anhydrase II during reperfusion is found to ameliorate ischemia reperfusion injury
separately. An attempt is made to synthesize dual inhibitors of sodium hydrogen exchanger and
carbonic anhydrase to have better potential drug molecule in ischemia reperfusion injury treatment.
The hydroxybenzotriazole is considered as a central pharmacophore for this dual activity and 12
derivatives are synthesized. All derivatives are tested for sodium hydrogen exchanger I and carbonic
anhydrase II inhibitory activity. The tosylate derivative (12) is found to be the most potent
derivative with IC50 158.7± 8.4 μM for carbonic anhydrase II and 31.07 ± 1.06 μM for sodium
hydrogen exchanger I. Although the potency is less than standard drugs but this is the first report
of dual inhibitor of carbonic anhydrase II and sodium hydrogen exchanger.