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Novel Antibacterial Scaffold from Natural Products

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2011 / SBIR
Agency Tracking Number:
R43AI096847
Solicitation Year:
2011
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
LIFEPHARMS, INC.
143 Shaw Street New London, CT 06320-
View profile »
Woman-Owned: No
Minority-Owned: Yes
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2011
Title: Novel Antibacterial Scaffold from Natural Products
Agency: HHS
Contract: 1R43AI096847-01
Award Amount: $600,000.00
 

Abstract:

DESCRIPTION (provided by applicant): Despite the rise of bacterial resistance to antibiotics, the development of new antibiotics is on the decline. Methicillin-resistant Staphococcal aureus infections (MRSA) in the United States has been increasing, causing 19,000 deaths per year in the United States and contributing to 3 billion to 4 billion of additional annual health care costs. The issue of combating resistance has been exacerbated by the relative scarcity of new chemical scaffolds discovered or developed. Most of the antibacterial research at pharmaceutical companies has been towards developing analogs of existing drugs through traditional chemistry driven SAR programs. Very few new classes of antibiotics have been introduced in the past decades, andmost antibiotics act on familiar targets. In addition, even though natural products have been a rich source of new antibacterials, many pharmaceutical companies have natural product libraries that have been thoroughly screened and offer little in the way of diversity or novelty. There is a growing awareness that natural product libraries, particularly those with a fungal origin, need to exploit fungal cryptic or secret pathways that normally are not expressed in laboratory conditions. To exploit the largely undiscovered secondary metabolites of mushrooms (basidiomycetes and ascomycetes), LifePharms, Inc. has established a collection of field- collected, environmentally challenged fruiting bodies. LifePharms/Microbiotix collaboration has identified, purified, and characterized two compounds that exhibit potent antibacterial activity (MICs as low as 0.5 5g/ml) against Gram-positive pathogens, including MSSA, MRSA, MRSE, and VRE, and favorable cytotoxicity profiles (CC50 gt 100 5g/ml). The chemical structures of these two lead compounds indicate they are novel antibacterial compounds. In addition, we have purified and partially characterized three more potent antibacterial compounds that will serve as alternative scaffolds. In this Phase I grant, we will i) evaluate these compounds in a series of in vitro assays that will measure ADMET, ii) chemically optimize these compounds by generating analogs using semi-synthetic methodologies to determine structure activity relationships and to improve potency and selectivity, iii) Data obtained from these assays will inform the design of subsequent analogs, resulting in an iterative process of analog design and evaluation, to improve the efficacy, selectivity, and ADMET properties of the scaffolds. In Phase II, compounds that meet the specified criteria for efficacy, selectivity, and ADMET properties will be tested for acute toxicity and antibacterial efficacy in mice. PUBLIC HEALTH RELEVANCE: Antibacterial infections with drug resistant organisms are a growing threat. LifePharms, Inc., and Microbiotix, Inc. have collaborated to discover structurally and mechanistically novel antibacterial compounds. These compounds are effective against several strains/species of drug resistant Gram (+) bacteria in vitro. The goal ofthis project is to pursue the preclinical development of these compounds as novel antibiotics.

Principal Investigator:

Esteban E. Mena
860-447-8583
lifepharms@aol.com

Business Contact:

Wendy P. Login
860-447-8583
lifepharms@aol.com
Small Business Information at Submission:

LIFEPHARMS, INC.
143 Shaw Street New London, CT 06320-

EIN/Tax ID: 106136910
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: Yes
HUBZone-Owned: No