Biological activity of antitumoural MGBG: the structural variable.
The present study aims at determining the structure-activity relationships (SAR's) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG's structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.
Marques
M P M
MP
Research Unit "Química-Física Molecular", University of Coimbra, Coimbra, Portugal. pmc@ci.uc.pt
Gil
F P S C
FP
Calheiros
R
R
Battaglia
V
V
Brunati
A M
AM
Agostinelli
E
E
Toninello
A
A
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D008935:Mitoguazone / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D008958:Models, Molecular; D011789:Quantum Theory; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013096:Spermine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013096:Spermine; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D002118:Calcium; D013095:Spermidine