Metabolism of halogenated bisphosphonates by the cellular slime mould Dictyostelium discoideum.
Methylenebisphosphonate and its monofluoro-, difluoro- and dichloro- derivatives inhibited growth of amoebae of Dictyostelium discoideum. Dichloromethylenebisphosphonate was the most potent inhibitor of amoebal growth whereas difluoromethylenebisphosphonate was the least potent inhibitor. Each of the bisphosphonates was taken up by the amoebae and incorporated into the corresponding beta, gamma-methylene analogue of adenosine triphosphate. Two of the bisphosphonates were also incorporated into the corresponding analogues of diadenosyl tetraphosphate. No correlation was found between the ability of the bisphosphonates to inhibit amoebal growth and the extent to which they were metabolised.
Rogers
M J
MJ
Krebs Institute, Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
Russell
R G
RG
Blackburn
G M
GM
Williamson
M P
MP
Watts
D J
DJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004023:Dictyostelium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011756:Diphosphates / Q000378:metabolism; D004164:Diphosphonates / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
D011756:Diphosphates; D004164:Diphosphonates; D000255:Adenosine Triphosphate