14 March 2018
New class of potent antibiotics engineered from old
Published online 1 June 2015
New modifications into old antibiotics can treat stubborn infections, says fresh research.
An old, ineffective class of antibiotics has been re-engineered into a powerful series of second-generation drugs which have the potential to treat a variety of antibiotic resistant infections.
A team of international researchers - including a microbiologist from Egypt’s Cairo University - modified part of the core of the antibiotic, spectinomycin, to add what the researcher called a “chemical hook."
This “hook” enabled the new class of antibiotics, called N-benzyl amino methyl spectinomycins, to more effectively kill bacteria, most likely through increased penetration and retention in bacterial cells, explains study co-author and chemical biologist Richard Lee of St. Jude Children’s Research Hospital in the U.S.
Spectinomycin, first developed in the 1960s, works by binding to a distinct site in the bacteria’s molecular machine (or ribosome) and disrupting protein synthesis. Although the drug had an excellent safety record, it was found to have only moderate antibacterial properties.
There is much further preclinical development work to do to ensure safety of this series.
The new compounds were found to continue to disrupt protein synthesis by acting on the bacterial ribosomes, while also showing increased potency against four upper respiratory tract infections and the sexually transmitted bacterial diseases chlamydia and gonorrhea.
The lead compound in the series cured mice of potentially fatal pneumococcal pneumonia and sepsis in relatively small doses. It also demonstrated low risk for adverse reactions or drug-to-drug interactions.
“There is much further preclinical development work to do to ensure safety of this series and to select the best dosing regimen to move ultimately into clinical trials,” says Lee.
Synthetic modification of validated antibiotics has been one of the most successful strategies in antibacterial drug discovery, the researchers say.