Clofazimine analogues active against a clofazimine-resistant organism.
Clofazimine analogues active against a strain of Mycobacterium smegmatis 607 made resistant to the antileprosy agent have been synthesized. Activity (i.e., less than or equal to 2 micrograms/mL causing complete inhibition of growth) requires that there be a basic nitrogen in the "rimino" side chain and that the spacer distance between this nitrogen and the imino nitrogen be at least three carbon atoms. The nitrogen may be primary, secondary, or tertiary and may be part of an open chain or enclosed in a ring compound. Provided that the criteria of basicity and spacer distance are satisfied, all are active in vitro against both the sensitive and resistant strains. Substitution elsewhere in the molecule had little effect on the activity. The compounds have been shown to have growth inhibitory activity against human-derived Mycobacterium leprae in murine macrophages in culture.
O'Sullivan
J F
JF
Medical Research Council of Ireland Laboratories, Trinity College, Dublin.
Conalty
M L
ML
Morrison
N E
NE
D000818:Animals; D002478:Cells, Cultured; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009161:Mycobacterium / Q000187:drug effects*; D009166:Mycobacterium leprae / Q000187:drug effects; D013329:Structure-Activity Relationship
D002991:Clofazimine