Bis(alkylamino)anthracenedione antineoplastic agent metabolic activation by NADPH-cytochrome P-450 reductase and NADH dehydrogenase: diminished activity relative to anthracyclines

Archives of Biochemistry and Biophysics
E D Kharasch, R F Novak

Abstract

Stimulation of the rates of NAD(P)H oxidation, superoxide generation, and hydrogen peroxide formation by three anthracenedione antineoplastic agents in the presence of NADPH-cytochrome P-450 reductase, NADH dehydrogenase, or rabbit hepatic microsomes was studied and the results compared with those obtained for the anthracyclines Adriamycin and daunorubicin. In all cases the anthracenediones, including mitoxantrone and ametantrone, were significantly (5- to 20-fold) less effective than the anthracyclines in stimulating NAD(P)H oxidation, superoxide formation, or hydrogen peroxide production. Of the three anthracenediones studied, the ring-monohydroxylated compound showed the greatest activity followed by the ring-dihydroxylated derivative (mitoxantrone). In contrast, the non-ring-hydroxylated anthracenedione (ametantrone) was a relatively ineffective electron acceptor and inhibited the reduction of more effective acceptors such as Adriamycin. Michaelis-Menten kinetic constants were determined by analysis of the rates of NADPH oxidation. NADP+ and 2'-AMP inhibited the reduction of the ring-hydroxylated anthracenediones and anthracyclines, demonstrating the enzymatic nature of the reaction. The non-ring-hydroxylated anthracenedion...Continue Reading

References

Jul 25, 1977·Biochemical and Biophysical Research Communications·J Goodman, P Hochstein
Feb 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·N R BachurH Kon
Jul 1, 1979·Archives of Biochemistry and Biophysics·J S French, M J Coon
Jul 22, 1975·Biochemical and Biophysical Research Communications·A AzziC Richter
Dec 1, 1977·Chemico-biological Interactions·W S Thayer
Mar 1, 1979·Journal of Pharmaceutical Sciences·C C ChengR K Zee-Cheng
Sep 1, 1979·Journal of Medicinal Chemistry·K C MurdockR V Citarella
Sep 1, 1976·Cancer Treatment Reviews·L Lenaz, J A Page
Dec 1, 1975·Journal of the National Cancer Institute·S K Carter
Feb 1, 1981·Biochemical Pharmacology·J H Doroshow, J Reeves
Jun 1, 1981·Archives of Biochemistry and Biophysics·C C Winterbourn
Jul 16, 1981·The New England Journal of Medicine·R C YoungC E Myers
Nov 1, 1981·Archives of Biochemistry and Biophysics·E D Kharasch, R F Novak
Jan 1, 1980·Cancer Chemotherapy and Pharmacology·D S AlbertsE Murray
Aug 1, 1955·Biochimica Et Biophysica Acta·E F NEUFELDS P COLOWICK

❮ Previous
Next ❯

Citations

Jan 1, 1987·Pharmacology & Therapeutics·G Powis
Aug 1, 1990·Toxicology·S F Llesuy, S L Arnaiz
Jan 1, 1988·Free Radical Biology & Medicine·P KolodziejczykJ W Lown
Jan 1, 1989·Free Radical Biology & Medicine·G Powis
Dec 24, 2013·European Journal of Drug Metabolism and Pharmacokinetics·Jinhui XuYun Chen
Dec 1, 1985·Environmental Health Perspectives·B R Abdella, J Fisher
Apr 15, 1989·Biochemical Pharmacology·S J Duthie, M H Grant
Jan 1, 1990·Chemico-biological Interactions·B Nguyen, P L Gutierrez
Jun 28, 2016·Archives of Toxicology·Roberto Marques DamianiJenifer Saffi
Jan 1, 1989·Free Radical Research Communications·G R FisherL H Patterson
Jan 7, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Abraham Chang
Nov 27, 1991·Biochemical Pharmacology·J L PrekegesK H Krohn
Aug 1, 1991·Toxicology and Applied Pharmacology·J F Ghersi-EgeaG Siest

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.