 Antibiotic resistance is a growing global health threat, requiring urgent attention. One approach to overcome this problem is to discover and develop new antibiotic enhancers, molecules that can work with existing antibiotics to increase their effectiveness against resistant bacteria. In our previous study, we screened a library of purified marine natural products and their synthetic analogues and discovered an endoglioxal spermine derivative that had intrinsic antimicrobial properties and could also potentiate the action of doxycycline towards the difficult-to-treat gram-negative bacterium pseudomonas aeroginosa. We then created a series of analogues, exploring the influence of indole substitution at the five and seven positions and the length of the polyamine chain on biological activity. While some analogues showed limited cytotoxicity and or hemolytic activity, two seven-methyl-substituted analogues, 23b and 23c, were found to be strong inhibitors of gram-positive bacteria without any detectable cytotoxicity or hemolytic properties. This article was authored by Melissa M. Kade-Lease, Tim Lu, Kenneth Sue, and others. We are article.tv, links in the description below.