Inhibition of succinate-cytochrome C reductase by a ferromacrocyclic complex.
Succinate-cytochrome c reductase (SCR) from mouse liver was inhibited strongly and reversibly by an iron (II) macrocyclic complex 3. The inhibition was observed for the enzyme toward the reduction of both 2,6-dichlorophenol indophenol (DCIP) and cytochrome c (cyt c). The inhibition was a mixed type and noncompetitive with respect to the reduction of DCIP and cyt c, respectively. Values of the inhibition constant ranged from 6.6 to 8.3 microM. The IC50 for the complex 3 was found to be 16.6 +/- 0.8 and 12.1 +/- 0.5 microM for the enzyme toward DCIP and cyt c, respectively. The reduced form of complex 3 also exhibited enzyme inhibition but to a less extent. Complex 3, at a lower level, equal to 25% of its LD50 showed about 50% inhibition of the enzyme through in vivo dose-dependent effect. These findings suggested that the structure of the equatorial benzoquinoid macrocyclic ligand of the Fe(II) complex is involved in the enzyme inhibition.
Balbaa
M
M
Department of Biochemistry, Faculty of Science, Alexandria University, Egypt. m_balbaa@hotmail.com
Khalifa
M
M
el-Sabawaya
M
M
Kandeel
K
K
D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006418:Heme / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D051379:Mice; D018716:Molecular Mimicry; D013329:Structure-Activity Relationship; D013384:Succinate Cytochrome c Oxidoreductase / Q000037:antagonists & inhibitors*; D015996:Survival Rate
D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D008024:Ligands; D006418:Heme; D013384:Succinate Cytochrome c Oxidoreductase