AUTHOR=Kusy Damian , Marchwicka Aleksandra , Małolepsza Joanna , Justyna Katarzyna , Gendaszewska-Darmach Edyta , Błażewska Katarzyna Magdalena 

TITLE=Synthesis of the 6-Substituted Imidazo[1,2-a]Pyridine-3-yl-2- Phosphonopropionic Acids as Potential Inhibitors of Rab Geranylgeranyl Transferase

JOURNAL=Frontiers in Chemistry

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.596162

DOI=10.3389/fchem.2020.596162

ISSN=2296-2646

ABSTRACT=<p>Twelve phosphonopropionates derived from 2-hydroxy-3-imidazo[1,2-<italic>a</italic>]pyridin-3-<italic>yl</italic>-2-phosphonopropionic acid (3-IPEHPC) were synthesized and evaluated for their activity as inhibitors of protein geranylgeranylation. The nature of the substituent in the C6 position of imidazo[1,2-<italic>a</italic>]pyridine ring was responsible for the compound's activity against Rab geranylgeranyl transferase (RGGT). The most active inhibitors disrupted Rab11A prenylation in the human cervical carcinoma HeLa cell line. The esterification of carboxylic acid in the phosphonopropionate moiety turned the inhibitor into an inactive analog.</p>