Carbonic anhydrase VII: Development of selective inhibitors and their pharmacological significance

Human carbonic anhydrase VII (hCA VII) is a cytosolic zinc metalloenzyme largely expressed in the brain, where it plays an important role in regulating intracellular pH. hCA VII emerged as a valuable therapeutic target for epilepsy and other neurological disorders due to its involvement in neuronal excitability and seizure generation. We provide a comprehensive outline of the structural features, physiological functions, and pathological significance of hCA VII. Recent advances in medicinal chemistry research, aimed at developing selective hCA VII inhibitors, are discussed in detail, including drug design strategy, structure-activity relationship, and inhibitory activity. Numerous classes of compounds, such as sulfonamides, sulfamides, and various heterocyclic scaffolds, have been widely used to develop effective and selective hCA VII inhibitors. The pharmacological actions of the developed hCA VII inhibitors, including antiepileptic, neuroprotective, and other neurological effects, are also discussed in detail, together with hCA VII activators. Overall, we highlight the therapeutic potential of hCA VII as a target for treating several neurological disorders, including epilepsy, providing valuable guidance for the future design of therapeutic molecules targeting it.