INV-1253
Historically, natural products and microorganisms have been considered as the major sources of new pharmaceutical compounds. However, in recent years, there has been a dramatic drop in natural-based drug discovery from big pharmaceutical companies. The major challenges are the prevailing paradigm for drug discovery in large pharmaceutical industries, and the technical limitations in identifying new compounds with desirable activity.
The prevailing paradigm uses high throughput screening (HTS) methods. HTS of natural sources results in the rediscovery of known compounds, identifying a very small number of potential compounds.
To address this challenge, dereplication methods are performed on samples of interest. Current methods for dereplication such as analytical separation, followed by mass spectrometry, are time-consuming, resource-intensive, and prohibitively expensive.
Researchers at Northeastern developed a simple efficient method to identify new pharmaceutical compounds in one step. In this method, they developed a panel of microbial strains that are resistant to all known antimicrobial agents. As a new molecular candidate is applied to the panel, the suppression in the growth of resistant microbes reveals new antimicrobial properties for the unknown compound. The panel is in the form of a miniaturized version of standard microtiter plates, built with microfluidic technology, and containing thousands of wells. Each well consists of a monoculture of microbial species that is resistant to one or more antimicrobial agents. After exposure of the plate to new compounds, the plate is analyzed either under the microscope or in a plate reader. This technology overcomes the current limitations of methods used for the discovery of new antimicrobial agents. Also, it can be used to discover new compounds with anti-inflammatory and anticancer properties from natural resources.