New inhibitors may offer novel approach to treating deadly tuberculosis

Purdue University innovators have developed highly potent and selective compounds for use in the treatment of tuberculosis, which is one of the top 10 causes of death worldwide.

The Purdue researchers developed a series of small molecule inhibitors to target one of the proteins critical for the survival of TB in infected macrophages. Protein tyrosine phosphates B (mPTPB) is a virulence factor of TB to subvert the host immune responses.

The Purdue research is published in the Journal of Medicinal Chemistry.

"The death toll from TB is particularly high because of drug-resistant strains," said Zhong-Yin Zhang, distinguished professor and head of Purdue's Department of Medicinal Chemistry and Molecular Pharmacology and director of Purdue Institute for Drug Discovery. "These inhibitors are part of a promising new approach to developing TB therapeutic agents with novel targets and mechanisms of action to help save more lives."

Current treatments for TB are mostly antibiotic-based solutions. A major problem is that a large number of patients fail to take the entire antibiotic regime, which can lead to drug-resistant strains.

"We developed a platform to target mPTPB for novel anti-TB agents that builds on technologies we pioneered to modulate abnormal protein tyrosine phosphatase activity for the treatment of diseases such as cancer, diabetes and autoimmune disorders," Zhang said.

Zhang said these inhibitors' properties also make them promising drug candidates. They possess lighter molecular weights, excellent metabolic stability and bioavailability to provide a starting point for further therapeutic development for use as TB treatments.