Isoindolinones as Antimicrobial Agents

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43AI078646-01
Agency Tracking Number: AI078646
Amount: $225,624.00
Phase: Phase I
Program: SBIR
Awards Year: 2008
Solicitation Year: 2008
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Small Business Information
DUNS: 130194082
HUBZone Owned: Y
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Principal Investigator
 () -
Business Contact
Phone: (406) 884-0022
Research Institution
DESCRIPTION (provided by applicant): Antibiotic resistance among common pathogens is a serious public health problem because it compromises our ability to treat many infectious diseases. The problem has been compounded by the lack of discovery of new antib iotics that act in novel ways. Such compounds are critically needed as bacterial resistance to older antibiotics, and even their newer derivatives, is growing. The goal of our work is to develop a new set of antibacterial compounds that we have discovered, the isoindolinone derivative, as agents that are active against Gram-positive pathogens. In this Phase I SBIR feasibility study we ask a simple question: Can we demonstrate that our novel isoindolinone compounds have a good potential to lead to a new anti bacterial drug? We will determine the general mechanism of action of our current lead compound. We will also prepare additional analogs to identify the general structural activity relationship of our isoindolinone derivatives. Our studies will show if we a re able to prepare selective and druggable compounds suitable for further development in a Phase II study. Specifically, we plan to determine the mechanism of action of the isoindolinone class by determining if our lead compound perturbs the synthesis rate s of protein, RNA, and DNA. We will also assess the ability of our lead compound to induce resistance and determine the synergy and antagonism of our lead compound with antibiotics of known mechanism of action. We will also prepare a highly focused set of analogs of our lead compound, in order to determine an optimal substitution pattern around a key aromatic ring. PUBLIC HEALTH RELEVANCE: The ability to treat bacterial infections has become compromised by a growing resistance among common bacteria to antib iotics; this has become a significant public health problem. We have identified a novel structural class of antibacterial agents, and will study the mechanism of action and prepare a select set of analogs to evaluate for antibacterial activity. If successf ul, this project will provide a new class of antibacterial agents to combat the problem of antibiotic resistance.

* information listed above is at the time of submission.

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