Isocitrate Lyase: A Potential Target for Anti-Tubercular Drugs

Rohit      Sharma; Oisik      Das; Satyawan G.      Damle; Anil K.      Sharma

Abstract

Current TB regimen involves a combination of first and second line drugs which target only a small number of core metabolic processes such as deoxyribonucleic acid (DNA)/ ribonucleic acid (RNA) synthesis, cell wall synthesis, and energy metabolism pathways. New classes of drugs with additional drug targets that are resistant to mutation are an urgent necessity. Novel targets involved in vital aspects of bacterial growth, metabolism and viability and whose inactivation would lead to bacterial death or an inability to persist need to be investigated. Isocitrate lyase (ICL), which catalyses the first step in the glyoxylate cycle is found to play a pivotal role in persistence of Mycobacterium tuberculosis in mice, can be a potential target for anti-tubercular drug. The current review provides a detailed overview of the therapeutic potential, patents and recent advancements in the investigative studies done on isocitrate lyase (ICL) as an antitubercular drug target. Salicylanilide, benzanilide, 3-nitropropionamide and pthalazinyl derivatives, Pyruvate-isoniazid analogs and its copper complexes are among the synthesized compounds showing a great potential to inhibit mycobacterial ICL and a significant antimycobacterial effect. Some of the relevant patents in the ICL research have been further reviewed and discussed.

Keywords: Isocitrate lyase, Mycobacterium tuberculosis, inhibition, persistence.

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