A novel agent effective against Clostridium difficile infection

Abstract

N(2)-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase of Clostridium difficile. MorE-DCBG and its analogs strongly inhibited the growth of a wide variety of C. difficile strains. When administered orally in a hamster model of C. difficile-specific colitis, 362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease.

Figures

Fig 1

Structures of 7-(morpholinyl)alkyl-DCBGs.

Fig 2

Acute cures and recurrences of CDAD in hamsters treated with 362E or vancomycin. Oral infection was on day 0 with 0.5 × 107 CFU of C. difficile strain ATCC 43255. The setup for the basic experimental protocol is described in the text. 362E (green squares) or vancomycin (red circles) was given twice daily at 50 mg/kg/dose by oral gavage from days 1 to 3, and, in separate groups, 362E was given by oral gavage from days 1 to 7 (green triangles) or 1 to 14 (open squares). Blue circles, untreated control animals.