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Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Doxorubicin (see next scheme), isolated from the soil bacterium Streptomyces peucetius and structurally closely related to Daunorubicin and Epirubicin is one of the most important chemotherapeutic antitumor drugs, a cytotoxic anthracycline. Its antineoplastic activity relies on the intercalation between base pairs in the DNA helix (adducts between guanine and DOX) with the consequence of impaired DNA replication and protein synthesis. Furthermore, DOX is a topoisomerase II inhibitor; topoisomerase is involved in a variety of nuclear processes such as DNA replication, transcription, etc. Finally, DNA damage and cell death is caused by an oxidation of the quinone structure of the iron chelator DOX through a variety of NAD(P)H-oxidoreductases resulting in the generation of semiquinone radicals reacting with oxygen to superoxide and hydrogen peroxide; complexes formed between DOX and Fe catalyze the conversion of hydrogen peroxide to highly reactive hydroxyl radicals. This drug-induced release of free radicals causes oxidative stress that contributes to the toxicity of the anthracycline antibiotics (Yang et al., 2014; Agudelo et al., 2014). Increased levels of reactive oxygen species and lipid peroxidation are among others also responsible for DOX’s cardiotoxicity (Chatterjee et al., 2010, and literature cited therein).
Mechanisms of Different Anticancer Drugs
Published in Anjana Pandey, Saumya Srivastava, Recent Advances in Cancer Diagnostics and Therapy, 2022
Anjana Pandey, Saumya Srivastava
Daunorubicin and adriamycin are the anticancerous antibiotics that belong to the anthracycline group. These antibiotics are structurally similar and isolated from the fungus culture, i.e., Streptomyces peucetius (Edwardson et al., 2015). Both of these drugs have shown their clinical potential against lymphomas, leukemia, and a number of other tumors. These antitumor drugs show collective dose-dependent cardiomyopathy. Both drugs show a similar mode of action, i.e., blockage of nucleic acid synthesis. Their high-affinity binding with DNA by intercalation has been shown in different studies. These antitumor drugs show maximum toxicity during the synthetic phase of DNA (Marinello et al., 2018).
Contributions of Recombinant Microbes and Their Potential
Published in Yoshikatsu Murooka, Tadayuki Imanaka, Recombinant Microbes for Industrial and Agricultural Applications, 2020
Arnold L. Demain, Akira Kimura, Atsuhiko Shinmyo
Substantial overproduction (up to sevenfold) of daunorubicin was achieved by cloning of DNA fragments encoding daunorubicin biosynthetic genes into producing cultures of Streptomyces peucetius, S. peucetius subsp. caesius, and a blocked mutant [92].
Nuclear targeting peptide-modified, DOX-loaded, PHBV nanoparticles enhance drug efficacy by targeting to Saos-2 cell nuclear membranes
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Ayla Şahin, Gozde Eke, Arda Buyuksungur, Nesrin Hasirci, Vasif Hasirci
Chemotherapy has been a major therapeutic approach for the treatment of cancer. Doxorubicin (DOX) is a widely used anticancer agent for bone cancer treatment and has also shown activity against the solid tumors with its action inside the nucleus. It has an anthracycline structure and is isolated from a soil bacterium, Streptomyces peucetius. In general, anthracycline drugs prefer to intercalate the DNA base pairs that are connected to sugar moieties in the DNA minor groove and prevent resealing of DNA during the replication and transcription, and interrupt cell division. DOX interacts with both healthy and cancerous cells causing undesirable side effects. Nanotechnology is an approach that could increase the activity of DOX by maximizing its effect by concentrating it at the cancerous tissue and minimizing its damage to healthy sites [11,12].
Fabricating of Fe3O4@Ag-MOF nanocomposite and evaluating its adsorption activity for removal of doxorubicin
Published in Journal of Environmental Science and Health, Part A, 2022
N. M. El-Metwaly, H. A. Katouah, M. G. El-Desouky, A. A. El-Bindary, M. A. El-Bindary
Doxorubicin is an anthracycline antibiotic with anti-cancer activity. Doxorubicin was produced by the bacteria Streptomyces peucetius var. and is the hydroxylated congener of daunorubicin. caesius. Doxorubicin suppresses protein synthesis to stop DNA replication, the DNA helix is intercalated between base pairs. Doxorubicin also inhibits topoisomerase II, enhancing the consistency of the enzyme-DNA complex during DNA replication and avoiding the ligation of the nucleotide strand following double-strand breaks. Doxorubicin also generates oxygen free radicals, which result in cytotoxicity because they peroxide the lipids in cell membranes. The impact of oxygen free radicals on the heart and blood arteries make the anthracycline antibiotics particularly dangerous.
Enhanced doxorubicin production by Streptomyces peucetius using a combination of classical strain mutation and medium optimization
Published in Preparative Biochemistry and Biotechnology, 2018
Xiaoru Wang, Xiaorong Tian, Yuanjie Wu, Xiaofang Shen, Songbai Yang, Shaoxin Chen
Doxorubicin (DXR) is an anthracycline-type antibiotic that was first isolated from Streptomyces peucetius ATCC 27952 and is widely used to treat various cancers.[1] Although DXR is a microbial metabolite of S. peucetius ATCC 27952, due to its low yield it is currently produced commercially via semi-synthesis from its precursor, daunorubicin.[2] However, chemical synthesis of DXR has many disadvantages, including low product yield, high manufacture costs, and environmental pollution. If DXR could be efficiently produced by S. peucetius via direct fermentation, it would likely be a more cost-effective and environmentally-friendly process.