Structure-activity relationships, kinetics, selectivity, and mechanistic studies of synthetic hydraphile channels in bacterial and mammalian cells.
Hydraphile compounds are shown to be cytotoxic to Gram-negative and Gram-positive bacteria, yeast, and mammalian cells. Their cellular toxicity compares favorably with other synthetic ionophores and rivals that potency of natural antibiotics. The effects of structural variations on toxicity are described. The effects of these variations correlate well with previous studies of ion transport in liposomes. Whole cell patch clamping with mammalian cells confirms a channel mechanism in living cells suggesting that this family may comprise novel and flexible pharmacological agents.
Leevy
W Matthew
WM
Department of Molecular Biology & Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. ggokel@wustl.edu.
Gammon
Seth T
ST
Levchenko
Tatiana
T
Daranciang
David D
DD
Murillo
Oscar
O
Torchilin
Vladimir
V
Piwnica-Worms
David
D
Huettner
James E
JE
Gokel
George W
GW
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000378:metabolism*; D002478:Cells, Cultured; D007473:Ion Channels / Q000138:chemical synthesis* / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013329:Structure-Activity Relationship; D013997:Time Factors; D015003:Yeasts / Q000378:metabolism*
D000890:Anti-Infective Agents; D007473:Ion Channels; D008081:Liposomes