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 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.

Inhibition of mammalian aspartate transcarbamylase by quinazolinone derivatives

“…Detection of the reversibility of binding of compounds 2 and 3 to ATCase. The reversibility of binding of each compound to ATCase was studied as described before for other enzymes [38,39]. Briefly, 1.0 mL of 0.2 mM of each compound was added to 1.0 mL of the enzyme for 60 min at room temperature and the mixture was then put in a cellophane bag.…”

Succinate cytochrome c reductase in schistosomiasis: in vitro inhibition by some schistosomicidal drugs

“…It is associated with various degrees of hepatic dysfunction and severe cases of infection can be fatal [10,12]. It has been reported that changes in some enzymes occur during S. mansoni infection and these enzymes belong to different classes of classification [1,2,14,17].…”