September 01, 2016


 Study produces hundreds of antimicrobial candidates

​Posted Aug. 17, 2016

A research group developed and used a macrolide antimicrobial discovery system to produce more than 300 drug candidates, according to a scientific article.

Most of the compounds tested had demonstrable antimicrobial activity, the article states. Two of the most promising ones were more potent than any approved macrolides against challenging strains of Streptococcus pneumoniae, vancomycin-resistant Enterococcus organisms, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa.

The article, “A platform for the discovery of new macrolide antibiotics,” was published May 19 (Nature 2016;533:338-345) and was based on work by researchers in Harvard University’s Department of Chemistry and Chemical Biology. It describes the creation of a synthetic platform for preparing novel macrolides and a foundation for their manufacture.

“Using simple building blocks and a highly convergent assembly process, we have prepared more than 300 structurally diverse macrolide antibiotic candidates, as well as the approved drug telithromycin and the clinical candidate solithromycin,” the article states. “We have identified molecules with diverse macrocyclic scaffolds that exhibit potent activities against bacterial strains resistant to erythromycin, azithromycin, and other current antibiotics of different classes.”

The methods used in the study, the authors state, could be used to create thousands of drug candidates and accelerate discovery of therapeutic agents.

An article written by the same research group and published in June, “Development of a platform for the discovery and practical synthesis of new tetracycline antibiotics” (Curr Opin Chem Biol 2016;32:48-57), provides a history of research that led to a system for creating antimicrobials and the discovery of eravacycline, among other tetracycline drug candidates. Andrew G. Myers, PhD, leads the Harvard research group behind both articles and is a cofounder of Tetraphase Pharmaceuticals, which is conducting clinical trials on eravacycline.