Presentation Type

Poster Presentation - Campus Access Only

Abstract/Artist Statement

Best of GradCon Award Winner: Poster Presentations - STEM

Over the past several years the introduction of new antibiotic drugs on the pharmaceutical market has decreased yet antibiotic resistance in bacteria is still present and growing. The Center for Disease Control (CDC) estimates there are 2.8 million infections per year resulting in 35,000 deaths from antibiotic resistant microbes.1 It is imperative that new antibiotics are discovered, studied and introduced to the market as new antimicrobial resistance develops. Currently the CDC has designated 18 bacteria and fungi having resistance threats including methicillin-resistant Staphylococcus aureus (MRSA) and the fungus Candida auris. Nonactin, a macrotetrolide, is a fermentation product from Streptomyces griseus, and its precursor nonactate is a potential scaffold for novel antibiotics.2,3 The target of our novel nonactate antibiotics is still unknown and the selectivity between mammalian and bacterial cells is poor. DNA and proteins are chiral targets which have the potential to selectively bind to a complementary chiral compound, like nonactate. Initial extraction and methanolysis of the nonactin core will result with two nonactate isomers as a set of (+) and (-) enantiomers. The nonactate core though has four chiral centers resulting in several other potential stereoisomers. Two of the chiral centers can easily be set to different positions resulting in four stereoisomers and their four enantiomers. A stereoselective Mitsunobu reaction has been used to switch one chiral center resulting in a total of four isomers. Creating an enol of the using the neighboring carbonyl group which can be an intermediate to an inverted center potentially providing the other four isomers. Three compounds from out library will be prepared from each of these eight stereoisomers, and then tested against several strains of microbes. Variation in the minimum inhibitory concentrations (MIC) between the stereoisomers would strongly indicate a potential chiral target, while retained MIC values indicate that it is unlikely to be a chiral target. Indication of a chiral target will help with understanding where the drug is binding therefore the development and modification for increased selectivity.

Mentor Name

Nigel Priestley

schwartz_IMG_3939.MOV (547854 kB)
Video Presentation: Chiral Effects on Nonactate-scaffold based Antibiotic Activity

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Feb 28th, 5:00 PM Feb 28th, 6:00 PM

Chiral Effects on Nonactate-scaffold based Antibiotic Activity

UC North Ballroom

Best of GradCon Award Winner: Poster Presentations - STEM

Over the past several years the introduction of new antibiotic drugs on the pharmaceutical market has decreased yet antibiotic resistance in bacteria is still present and growing. The Center for Disease Control (CDC) estimates there are 2.8 million infections per year resulting in 35,000 deaths from antibiotic resistant microbes.1 It is imperative that new antibiotics are discovered, studied and introduced to the market as new antimicrobial resistance develops. Currently the CDC has designated 18 bacteria and fungi having resistance threats including methicillin-resistant Staphylococcus aureus (MRSA) and the fungus Candida auris. Nonactin, a macrotetrolide, is a fermentation product from Streptomyces griseus, and its precursor nonactate is a potential scaffold for novel antibiotics.2,3 The target of our novel nonactate antibiotics is still unknown and the selectivity between mammalian and bacterial cells is poor. DNA and proteins are chiral targets which have the potential to selectively bind to a complementary chiral compound, like nonactate. Initial extraction and methanolysis of the nonactin core will result with two nonactate isomers as a set of (+) and (-) enantiomers. The nonactate core though has four chiral centers resulting in several other potential stereoisomers. Two of the chiral centers can easily be set to different positions resulting in four stereoisomers and their four enantiomers. A stereoselective Mitsunobu reaction has been used to switch one chiral center resulting in a total of four isomers. Creating an enol of the using the neighboring carbonyl group which can be an intermediate to an inverted center potentially providing the other four isomers. Three compounds from out library will be prepared from each of these eight stereoisomers, and then tested against several strains of microbes. Variation in the minimum inhibitory concentrations (MIC) between the stereoisomers would strongly indicate a potential chiral target, while retained MIC values indicate that it is unlikely to be a chiral target. Indication of a chiral target will help with understanding where the drug is binding therefore the development and modification for increased selectivity.