Carbonic anhydrase in Plasmodium falciparum: A useful target for antimalarial drug designing and malaria blocking transmission compounds

Carbonic anhydrase is a metalloenzyme that catalyzes the reversible conversion of CO to bicarbonate, an essential metabolic component used by the malaria parasites for de novo synthesis of pyrimidines and the exflagelation of gametocytes inside the mosquito vector. Carbonic anhydrase is involved in the transport of bicarbonate. This enzyme participates in transport of bicarbonate inside and outside the cells to avoid an imbalance in the system CO /HCO -and alteration of pH in the interior of the cell as well as in the intercellular space. Therefore, inhibition of this enzyme either in the parasite or the insect vector, could lead to a decrease in replication and to the detriment and/or death of the parasite. Given the importance of carbonic anhydrase in the metabolism, development and survival of Plasmodium, it could be postulated that carbonic anhydrase inhibitors are both a therapeutic and a blocking transmission alternative. Previous studies have demonstrated the in vitro anti-Plasmodium activity of some inhibitors. However, it is necessary to determine their effectiveness to confirm its usefulness in the treatment or blocking malaria transmission and the mechanism by which these inhibitors are able to affect the development of the parasite in the mosquito vector. In this paper we present a review about the role of carbonic anhydrase in Plasmodium spp and using some specific inhibitors as a strategy for malaria treatment and transmission blocking strategy. Articles published in the past 59 years identified from bibliographic database (PubMed and ScienceDirect) and papers collected by the authors were included.