title: Redox regulation in malaria: current concepts and pharmacotherapeutic implications.
abstract: Malaria imposes a serious threat to human and becomes more prevalent due to the emergence of drug resistant parasite. Understanding of the underlying mechanism of drug resistance and identification of novel drug targets are key effective processes for the management of malaria. Malaria parasite is highly susceptible to oxidative stress but lives in a pro-oxidant rich environment containing oxygen and iron, which produce a large amount of reactive oxygen species. Management of oxidative stress in malaria parasite is tightly regulated through active redox and antioxidant defense systems. The elevation of oxidative stress as a result of inhibition of any component of this defense system leads to redox imbalance and ultimately parasite death. Therefore, redox system plays an indispensable role for the survival of parasite within the host. Identification of key molecules, which disrupt parasite redox balance by altering key redox reactions and promote oxidative stress in parasites, would be an effective approach to develop novel antimalarial drugs. During the last few decades, contributions by researchers around the globe provide even better understanding of redox biology of malaria parasite. Here, in this review, we are highlighting the knowledge gathered so far regarding the essential redox-active processes and their components in malaria parasite to overcome elevated oxidative insults. We have also given maximum efforts to enlist currently used redox-active antimalarials, their mode of action and pharmacotherapeutic implications.
authors.affiliation: Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India.
authors.forename: M
authors.initials: M
authors.lastname: Goyal
authors.forename: A
authors.initials: A
authors.lastname: Alam
authors.forename: U
authors.initials: U
authors.lastname: Bandyopadhyay
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D010088:Oxidoreductases; D005978:Glutathione