A single bite from a kissing bug that carries the parasite Trypanosoma cruzi can lead to death. Known as Chagas disease, this neglected tropical disease affects eight million people primarily in Central and South America every year. Concern about the disease is continually increasing, as insect vectors are moving north into the United States. Kissing bugs have been sighted as far north as Delaware and continue to move northward. Only one medication, benznidazole, is approved by the U.S. Food and Drug Administration (FDA) to treat Chagas disease; however, this one therapeutic is not enough to combat the disease. Not only does benznidazole have harsh side effects, it is very expensive and is only FDA-approved for emergency cases in children. Additionally, there are increasing accounts of treatment failures due to mutations in T. cruzi’s TcNTR gene, leading to benznidazole resistance. Since the kissing bug is steadily moving north and medications are limited, more treatment options are needed.<br/><br/>This research focuses on disqauramides, small molecule antiparasitic compounds that are anti-Chagastic. Our target disquaramides require low-cost reagents and utilize a key Sonogashira coupling step. Limited research functionalizing squaramides via Sonogashira coupling exists; however, our experiment shows that the Sonogashira mechanism is capable of adding bulky substituents to squaramides, hopefully increasing their effectiveness against T. cruzi. This study has created, confirmed, and optimized this synthetic method’s effectiveness by using 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy. To date, our Sonogashira coupling between an alkyne-containing squaramide and substituted halo phenyl esters has been optimized to a 51% isolated yield. Future work includes creating other compounds using Sonogashira synthesis and then testing them against the parasite in vitro with the help of the DNDi. While one kissing bug bite can lead to death, one compound can save a person's life.

The Sonogashira coupling of squaramides: A novel method for the synthesis of anti-Chagastic compounds

ACS Spring Meeting 2021

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