Enoyl reductase: One target, Two major Global Threats

Tuberculosis and Malaria are two major global threats; both account for 5 million deaths annually (mostly in developing countries). Despite the worldwide ravages of Tuberculosis and Malaria, chemotherapeutic regimens against these two diseases have remained largely unchanged. There is an urgent need to develop novel, effective, and affordable drugs to treat both diseases because the resistance has developed or is developing to existing therapy. Scientists around the world are seeking new ways to combat the two opportunistic pathogens.

Mycobacterium tuberculosis and Plasmodium Falciparum are causative agents of tuberculosis and malaria, respectively. Both organisms share enzymatic components of the type II fatty acid biosynthetic pathway (FAS-II). Enoyl acyl carrier protein reductase (ENR) is one of the key type II enzymes, has been repeatedly validated as an effective antimicrobial target (e.g., INH, diazoborines, triclosan, and thiolactomycin).

Triclosan, the ENR inhibitor, showed excellent activity against both organisms. Targeting ENR  with a new class of compounds may yield new drugs against these devastating pathogens.

The Future of Drug Discovery

 The new technologies promise to fill drug development pipelines with small-molecule candidates unfulfilled, so the pharmaceutical industry is currently undergoing rapid changes. They are moving aggressively into large molecule (biologics) drug development.

"Drug space” that is not part of the current drug development includes non-Lipinski NCEs, nanomedicines, nucleic acid-based drugs, etc. will include in the future. One of the major challenges for a medicinal chemist is to find small molecule inhibitors for protein-protein interactions.

Toxicophores Simplified

Toxicophore is a portion of a chemical structure (molecular functionalities) responsible for the toxic properties of a pharmacologically activity compound. Medicinal chemists study toxicophores to predict and replace the potential reactive moieties in the early drug development process to avoid the drug candidate's later-stage failure. A simplified version of the toxicophores is attached here.