Isoniazid Derivatives as Anti-Tubercular Agents: From Structural Design to Clinical Investigations

Tuberculosis (TB) is one of the fatal infectious diseases, making it one of the causes of death in the infectious mortality strata, and it is of prime concern globally. It is spread by a causative agent called Mycobacterium tuberculosis (Mtb) which gets ingressed within the host cells. The current clinical interventions have been associated with various limitations, such as a long treatment regimen (6 months), low lipophilicity of drugs to penetrate the bacterial cell, associated side effects and emerging incidence of multiple drug-resistant strains. Despite these limitations, Isoniazid (INH), a first-line agent, remains a drug of choice to date due to its effectiveness. However, INH is associated with poor penetration into the bacteria cell wall and ultimately leads to the low therapeutic distribution of drugs into the lungs.

Studies have shown that the structural modifications of INH by introducing more lipophilic moiety could lead to its better penetration into the bacterial cell wall resulting in better anti-TB activities.

This review updates various studies conducted on INH derivatives as anti-tubercular (Anti-TB) agents, including in silico and preclinical investigations. In addition, updates on clinical investigations of novel anti-TB molecules have also been highlighted.

The article focuses on the structural modification of various INH derivatives reported, including the in vitro studies and molecular modelling preclinical and clinical investigations of various INH derivatives.