Novel antibiotic candidates starve resistant bacteria by blocking vitamin supply
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Researchers at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) have developed synthetic drug candidates that block energy-coupling factor transporters in bacteria, cutting off vitamin supply and killing the cells. The compounds show potency against resistant bacteria and favorable stability in liver microsome assays, with activity confirmed in insect and zebrafish larvae.
The Drug Target
Bacteria rely on energy-coupling factor (ECF) transporters to import vitamins from their environment. Human cells lack these transporters, making them a selective target. A drug blocking ECF transporters would attack bacteria while leaving human cells largely unaffected, reducing side effects.
Compound Optimization
Starting from an earlier synthetic inhibitor, the HIPS team synthesized numerous variants to improve both potency and metabolic stability. Early candidates broke down too quickly in liver microsome tests. The breakthrough came with heterocyclic building blocks that enhanced both properties simultaneously, according to Dr. Mostafa Hamed.
In Vivo Validation
The new generation of molecules successfully combated bacterial infections in insect and zebrafish larvae, marking the first confirmation of activity in living organisms. The findings were published in two studies in the Journal of Medicinal Chemistry.
What's Next
The team plans further preclinical development, including testing in mammalian models. It remains unclear whether the candidates will advance to human trials or face unforeseen toxicity or resistance issues.
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Novel antibiotic candidates starve resistant bacteria by blocking vitamin supply
