Abstract: 2-n-propylquinoline (2-PQ) is a natural compound having interesting anti-leishmanial activities by the oral route but with a rapid elimination rate. 2-PQ is insoluble in water and therefore cannot be administered intravenously. In this study, water-soluble polymeric prodrugs of 2-PQ were synthesized for intravenous administration with the objective of treating patients having severe visceral leishmaniasis with recurrent vomiting. As 2-PQ has no functional groups for tethering onto a soluble polymer, two amine derivatives of 2-PQ, (E)-2-(3-(2-ammonioethoxy)-3-oxoprop-1-en-1-yl)quinolin-1-ium chloride (1) and (E)-2-(3-(2-ammonioethyl)amino)-3-oxoprop-1-en-1-yl)quinolin-1-ium chloride (2), were synthesized and characterized using 1 H and 13 C NMR, IR, and mass spectroscopy. Both compounds (1) and (2) were soluble in water. They were tethered onto oxidized polyglucose (PG) at ~ 20 wt% concentration via imine linkages susceptible to hydrolysis. In vitro release at 37 °C into phosphate buffer showed that around 75% of both the compounds was released in 24 h. The parent compounds and their conjugates were evaluated for their anti-leishmanial activity both in vitro, and in vivo in a Leishmania donovani/Balb/c mice model. In vitro, the most active compound was (1) with an IC 50 value of 5.67 ± 0.0.44 μg/mL against axenic and 8.34 ± 0.74 μg/mL against intramacrophage amastigotes. In vivo, both compounds (1) and (2) were less active at a dose of 10 mg/kg body weight showing a reduction in parasite burden of 30.2 and 21.7% respectively. The conjugates of (1) and (2) with PG were inactive in vivo. Probably, much higher concentrations of the conjugates and prolonged treatment times are necessary for potential anti-leishmanial activity. Lay Summary: 2-n-propylquinoline (2-PQ) is a natural compound having anti-leishmanial activities by the oral route but with a rapid elimination rate. 2-PQ is insoluble in water and therefore cannot be administered intravenously. As 2-PQ has no functional groups, two amine derivatives of 2-PQ were synthesized and conjugated to oxidized polyglucose. The parent compounds and their conjugates were evaluated for their anti-leishmanial activity both in vitro, and in vivo in a Leishmania donovani/Balb/c mice model. The new compounds were less active compared to AmBisome® both in vitro and in vivo and the conjugates were not active. Possibly, multiple injections and prolonged treatment durations are necessary for better in vivo response. © 2018, The Regenerative Engineering Society.