Compound Technology

TECHNOLOGY:
Anti-Bacterial Inhibitors of FtsZ

DESCRIPTION:
The development of resistance to anti-bacterial agents is a significant threat to the ability to treat diseases. As organisms develop resistance, new antibacterial agents are required. Ideally, these agents selectively target the physiology of the organism yet allow for action against a broad spectrum of organisms.

These novel compounds function by inhibiting bacterial cell growth in vitro and in vivo through interference with FtsZ activity. FtsZ, a protein that is widely found in bacteria, plays a central role in cell division making it an attractive target for anti-bacterial agents. The compounds have a broad range of anti-bacterial activity and may be used to target gram-positive or gram-negative bacteria as well as bacteria that are non-gram test responsive. These compounds have demonstrated efficacy against antibiotic-resistant strains of M. tuberculosis, Escherichia, Enterococcus, and Staphylococcus.

One compound (SRI-3072) showed inhibition of M. tuberculosis in infected mouse bone marrow macrophages. The concentrations effecting 90% and 99% reduction in mycobacterial growth after seven days were 0.12 mg/mL (EC90) and 1.42 mg/mL (EC99).

Structurally, these compounds lend themselves to formation of pharmaceutically acceptable salts to improve solubility. They may be linked to permeability enhancers to promote crossover of the bacterial cell wall. The compounds are suitable for oral or parenteral administration, and the final formulations may be in solid, semi-solid or liquid form.

DEVELOPMENT STATUS: Pre-clinical

PATENT PROTECTION: US Patent Application No. 60/393,680

REFERENCE NUMBER: S0254

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