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Sojourn of Nitrogenous Heterocycles as Promising Antileishmanial Agents: Medicinal Perspectives and Structure–Activity Relationship Studies

  • Bhupender Nehra,
  • Manoj Kumar,
  • Sumitra Singh,
  • Viney Chawla,
  • Pooja A. Chawla

摘要

Leishmania is a protozoal parasitic disease enlisted in neglected disease by World Health Organization (WHO) and caused by different leishmanial species. Due to the adverse-effects and drug resistance acquired by the numerous leishmanial species, design and development of novel drug candidates with improved antileishmanial effect and least cytotoxic action against healthy cells of body. Drug resistance is an indeed challenge primarily required to be tackled to promote the effectiveness of antileishmanial agents. In order to achieve maximal antileishmanial response without any significant loss towards normal human cells, researchers are focused on the development of heterocycle-based derivatives. Apart from antileishmanial action of nitrogenous heterocyclic motif, numerous tiny to bulkier substituents alter the biological potency at significant level. On the basis of unique interactions of very function group towards target sites, nitrogen containing heterocycles are keen antileishmanial molecules afforded remarkable interactions towards available leishmanial drug targets including DHFR, PTR1, 14 α-demethylase, LdMetAP1 and many more. There are many nitrogen containing heterocyclic scaffolds such as pyrazole, imidazole, triazole, pyridine, piperidine, indole, quinoline etc. with their vital role in the eradication of various species of leishmania. The present review aimed to afford ideas regarding structure activity relationship of reported nitrogenous antileishmanial agents for researchers enrolled to generate heterocycle-based novel antileishmanial agents with more efficacy and least adverse-effects.

Graphical Abstract