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

Twelve phosphonopropionates derived from 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-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-a]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.

Automated summary

The research showed that the nature of the substituent in the C6 position of the imidazo[1,2-a]pyridine ring significantly affects the activity of phosphonopropionates against Rab geranylgeranyl transferase. The most active inhibitors disrupted Rab11A prenylation in HeLa cells, but esterification of carboxylic acid in the phosphonopropionate moiety led to a loss of activity.