Pks 13 inhibitors-a promising target for future antitubercular agents

Tuberculosis is an infectious disease that has re-emerged in multiple/extensively resistant forms (MDR/XDR) since 1990's creating threat to the mankind. The marketed drugs are not fully effective on these forms as they suffer from serious side effects. Thus developing drugs targeting the novel targets is the need of the hour to treat the disease. Many novel targets have been identified and Polyketide synthase 13 (Pks 13) has emerged as one of the promising targets to treat the tuberculosis. It links the meromycolic acid (C-48-C-64) branch originating from FAS-II, and alpha -alkyl C-26 fatty acid branch originating from fatty acid synthase I (FAS-I) via Claisen condensation and helps in final formation of precursors of mycolic acid, the major component of Cell walls of M. tuberculosis. It has five domains viz Acyl Carrier Protein -Keto acyl Synthase-Acetyl Tranferase-Acyl Carrier Protein-Thioesterase [ACP-KS-AT-ACP-TE]. The ACP domain has two portions and one of them is adjacent to KS domain (N-terminal ACP) and C-terminal ACP resides beside of TE domain. The N-ACP domain and TE domains have active sites. Thus, efforts are made to design, synthesize and test the Novel Chemical Entities (NCE's) for their antitubercular activity with Pks 13 enzyme as a target. The benzofurans, thiophenes, coumestans and beta lactones have been identified as ligands blocking Pks 13 enzyme with promising antitubercular activity. This article summarizes these classes of Pks 13 enzyme inhibitors exhibiting potential antitubercular activity along with their limitations and discusses the future scope. [GRAPHICS]

Automated summary

Tuberculosis is a re-emerging infectious disease that poses a threat to mankind. The current drugs are not fully effective against multiple/extensively resistant forms, and have serious side effects. Developing drugs targeting novel targets, such as Polyketide synthase 13 (Pks 13), is essential for treating tuberculosis.