Dipyridamole and its derivatives modify the kinetics of the electron transport in reaction centers from Rhodobacter sphaeroides.
A well known vasodilator dipyridamole (DIP), 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, and its derivatives have recently been shown as potential co-activators (modulators) in the phenomenon of multidrug resistance (MDR) in cancer therapy. They inhibit the specific function of a transmembrane P-glycoprotein responsible for the ex-flux of anti-cancer drugs from tumor cells. To clarify molecular mechanisms of the anti-MDR activity of DIP and its two derivatives, RA25 and RA47, we have studied their effects on electron transport in reaction centers (RC) from purple photosynthetic bacteria Rb. sphaeroides, using RC as a model system. Increasing concentrations of DIP and RA47 progressively accelerate the back electron transfer from the primary quinone acceptor QA to the bacteriochlorophyll dimer Bchl2 (Bchl2+ -QA- recombination). In the absence of o-phenantroline, when both quinone acceptors QA and QB are involved in the electron transport, RA47 is more effective than DIP. DIP stabilizes the electron on the secondary quinone acceptor QB, the effect manifested as the retardation of Bchl2+ -QB- recombination. Effects of RA25 are negligible in all cases. The drugs are proposed to change the electron transport affecting the RC structural dynamics and the stabilization of the electron on quinone acceptors through modification of H-bonds in the system.
Knox
P P
PP
Biophysics Department, Biology Faculty, M.V. Lomonosov State University, Moscow, Russia.
Churbanova
I Y
IY
Lukashev
E P
EP
Zakharova
N I
NI
Rubin
A B
AB
Borissevitc
G P
GP
D001429:Bacteriochlorophylls / Q000378:metabolism; D003624:Darkness; D019281:Dimerization; D004176:Dipyridamole / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007700:Kinetics; D008027:Light; D045342:Light-Harvesting Protein Complexes; D008954:Models, Biological; D045322:Photosynthetic Reaction Center Complex Proteins / Q000187:drug effects / Q000378:metabolism*; D012242:Rhodobacter sphaeroides / Q000187:drug effects / Q000378:metabolism*
D001429:Bacteriochlorophylls; D045342:Light-Harvesting Protein Complexes; D045322:Photosynthetic Reaction Center Complex Proteins; D004176:Dipyridamole