In our search for new antibiotic adjuvants as a novel strategy to deal with the emergence of multi-drug resistant (MDR) bacteria, a series of succinylprimaquine-polyamine (SPQ-PA) conjugates and derivatives of a cationic amphiphilic nature have been prepared. Evaluation of these primaquine conjugates for intrinsic antimicrobial properties and the ability to restore the antibiotic activity of doxycycline identified two derivatives, SPQ-PA3-8-3 and SPQ-PA3-10-3 that exhibited moderately strong intrinsic activity against the Gram-positive bacteria Staphylococcus aureus and the yeast Cryptococcus neoformans. None of the analogues were active against the Gram-negative bacterium Pseudomonas aeruginosa. However, in the presence of a sub-therapeutic amount of doxycycline (4.5 µM), both SPQ-PA3-4-3 and the SPQ-PA3-10-3 displayed potent antibiotic adjuvant properties against P. aeruginosa, with MIC's of 6.25 µM. A series of derivatives were prepared to investigate the structure-activity relationship that explored the influence of both a simplified aryl lipophilic substituent and variation of the length of the polyamine scaffold on observed intrinsic antimicrobial properties and the ability to potentiate the action of doxycycline against P. aeruginosa.