Molecular-level strategic goals and repressors in Leishmaniasis-Integrated data to accelerate target-based heterocyclic scaffolds

Leishmaniasis is a complex of neglected tropical diseases caused by various species of leishmanial parasites that primarily affect the world's poorest people. A limited number of standard medications are available for this disease that has been used for several decades, these drugs have many drawbacks such as resistance, higher cost, and patient compliance, making it difficult to reach the poor. The search for novel chemical entities to treat leishmaniasis has led to target-based scaffold research. Among several identified potential molecular targets, enzymes involved in the purine salvage pathway include polyamine biosynthetic process, such as arginase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase, trypanothione reductase as well as enzymes in the DNA cell cycle, such as DNA topoisomerases I and II plays vital role in the life cycle survival of leishmanial parasite. This review mainly focuses on various heterocyclic scaffolds, and their specific inhibitory targets against leishmaniasis, particularly those from the polyamine biosynthesis pathway and DNA topoisomerases with estimated activity studies of various heterocyclic analogs in terms of their IC50 or EC50 value, reported molecular docking analysis from available published literatures.

Automated summary

Leishmaniasis is a neglected tropical disease that affects the poorest people and is caused by various leishmanial parasites. The limited availability of standard drugs for this disease, along with their drawbacks, such as resistance and high cost, makes it challenging to treat the poor. Research on novel chemical entities has focused on enzymes involved in the purine salvage pathway and DNA topoisomerases, which play vital roles in the survival of the parasite. This review explores the inhibitory targets of heterocyclic scaffolds against leishmaniasis, particularly in terms of their IC50 or EC50 values and molecular docking analysis.