Due to the lack of innovation in new antibiotic development, our world is in danger of experiencing widespread antibiotic resistance. This could lead to a crisis with no suitable drugs to combat bacterial infections. It is not shocking to see that the most virulent and antibiotic-resistant bacteria are Gram-negative. The presence of an additional lipopolysaccharide layer (outer membrane) makes the penetration of molecules into the bacteria difficult. This makes the porin channels on the outer membrane of Gram-negative bacteria the main entryway for the molecules. However, the penetration of molecules through porin channels is highly selective. Some antibiotics are not effective against Gram-negative bacteria only because they cannot penetrate the outer bacterial membrane. To tackle this issue, in the last years, siderophores have been investigated as drug delivery agents thanks to their ability to bypass selective porins. Siderophores are iron-chelating molecules secreted by bacteria to uptake iron from the environment. They do not have to go through the porins but are actively transported into bacteria. Antibiotic-siderophore conjugates (sideromycins) have been tested to be successful in delivering antibiotics inside Gram-negative bacteria. Therefore, our research is focused on the synthesis of Catenulobactin B, a newly discovered naturally occurring siderophore, and analogs to explore their potential to form sideromycins. After being isolated in 2018, Catenulobactin B demonstrated iron-chelating ability and moderate cytotoxicity against P388 murine leukemia cells. Attempts for the first total synthesis of Catenulobactin B and its analogs are currently underway. Once the synthesis is achieved, a series of sideromycins will be synthesized and tested for their antimicrobial activity.

Efforts towards total synthesis of catenulobactin B and its analogs and explorations into their applications in formation of sideromycins

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.