Inhibition of Succinate-cytochrome C Reductase by a Ferromacrocyclic Complex

Abstract

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 μM. The IC₅₀ for the complex 3 was found to be 16.6 × 0.8 and 12.1 × 0.5 μM 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.

Key Words:

• Reductase
• Inhibition
• Kinetic parameters
• Macro-cycles