Inhibition of succinate-cytochrome C reductase by a ferromacrocyclic complex. 2001

M Balbaa, and M Khalifa, and M el-Sabawaya, and K Kandeel
Department of Biochemistry, Faculty of Science, Alexandria University, Egypt. m_balbaa@hotmail.com

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005296 Ferrous Compounds Inorganic or organic compounds that contain divalent iron. Compounds, Ferrous
D006418 Heme The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013384 Succinate Cytochrome c Oxidoreductase An electron transport chain complex that catalyzes the transfer of electrons from SUCCINATE to CYTOCHROME C. It includes ELECTRON TRANSPORT COMPLEX II and ELECTRON TRANSPORT COMPLEX III. Succinate Cytochrome c Reductase
D015996 Survival Rate The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. Cumulative Survival Rate,Mean Survival Time,Cumulative Survival Rates,Mean Survival Times,Rate, Cumulative Survival,Rate, Survival,Rates, Cumulative Survival,Rates, Survival,Survival Rate, Cumulative,Survival Rates,Survival Rates, Cumulative,Survival Time, Mean,Survival Times, Mean,Time, Mean Survival,Times, Mean Survival

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