Targeting antioxidant defense system enzymes for Leishmaniasis treatment.

Leishmaniasis, caused by the genus Leishmania remains a significant global health challenge. Current chemotherapeutics have limitations in terms of drug resistance, toxicity, and limited efficacy. As most of the currently used chemotherapeutics are single-target drugs, the chances of drug resistance development are very high. To overcome this challenge, the polypharmacology approach to designing multiple molecular target drugs is becoming a promising approach against leishmaniasis. Parasite Leishmania has a unique redox defense system to maintain cellular oxidative stress that helps it survive inside the host oxidative environment generated by the host immune response. This evolutionary divergence of redox systems of Leishmania from the human host is ideal for therapeutic interventions. This review focuses on the currently used anti-leishmanial therapeutics limitations and considers antioxidant defense system as a potential drug target pathway. By focusing on these phylogenetically distinct and parasite-specific enzymes, polypharmacological drugs can be developed to inhibit multiple molecular targets, simultaneously increasing efficacy and reducing the potential for resistance while minimizing adverse effects on the human host. This paradigm, which moves from single target to multi-target shift, holds promise for more effective treatments.