Advertisement

Topics

The Effect of Antitumor Antibiotic Olivomycin A and Its New Semi-synthetic Derivative Olivamide on the Activity of Murine DNA Methyltransferase Dnmt3a.

07:00 EST 1st January 2019 | BioPortfolio

Summary of "The Effect of Antitumor Antibiotic Olivomycin A and Its New Semi-synthetic Derivative Olivamide on the Activity of Murine DNA Methyltransferase Dnmt3a."

Olivomycin A is a highly active antitumor drug that belongs to the family of aureolic acid antibiotics. The antitumor effect of olivomycin A is related to its ability to bind to the DNA minor groove in GC-rich regions as Mg2+-coordinated complexes. Characterization of cellular targets of olivomycin A and its mechanism of action is crucial for the successful application of this antibiotic in clinical practice and development of semi-synthetic derivatives with improved pharmacological properties. Previously, we have shown that minor groove ligands are able to disrupt the key epigenetic process of DNA methylation. In this paper, we have studied the impact of olivomycin A and its improved semi-synthetic analogue N,N-dimethylaminoethylamide of 1'-des-(2,3-dihydroxy-n-butyroyl)-1'-carboxy-olivomycin A (olivamide) on the functioning of de novo DNA methyltransferase Dnmt3a (enzyme that carries out methylation of cytosine residues in the DNA CG-sites in eukaryotic cells) using an in vitro system consisting of the murine Dnmt3a catalytic domain and a 30-mer DNA duplex containing four consecutive GC pairs. We have shown that olivomycin A and olivamide inhibit Dnmt3a with IC of 6 ± 1 and 7.1 ± 0.7 μM, respectively. Neither olivomycin A nor olivamide interfered with the formation of the specific enzyme-substrate complex; however, olivomycin A prevented formation of the covalent DNA-Dnmt3a intermediate that is necessary for the methylation reaction to proceed. The inhibitory effects of olivomycin A and olivamide can be explained by the disruption of the enzyme catalytic loop movement through the DNA minor groove (the reaction stage that precedes the covalent bond formation between DNA and the enzyme). The results of this work indicate the epigenetic contribution to the antitumor effect of aureolic acid group antibiotics.

Affiliation

Journal Details

This article was published in the following journal.

Name: Biochemistry. Biokhimiia
ISSN: 1608-3040
Pages: 62-70

Links

DeepDyve research library

PubMed Articles [16025 Associated PubMed Articles listed on BioPortfolio]

Quantification of 1D, a novel derivative of curcumin with potential antitumor activity, in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study in rats.

1 D is a novel derivative of curcumin and shows very promising antitumor activities in various cancer cell lines.

Synthesis and Biological Activity of Analogs of the Antifungal Antibiotic UK-2A. II. Impact of modifications to the macrocycle benzyl position.

UK-2A is an antifungal antibiotic produced by Streptomyces sp. 517-02. Derivatization of its picolinamide-OH to form the isobutyryl-acetal led to the discovery of fenpicoxamid (InatreqTM active) curre...

Efficient Semi-Synthesis of Natural δ-( R)-Tocotrienols from a Renewable Vegetal Source.

Recent studies have highlighted the biological potential of tocotrienols, a vitamin E subfamily. The major natural sources of tocotrienols are complex mixtures requiring particularly challenging purif...

A new synthetic derivative of cryptotanshinone KYZ3 as STAT3 inhibitor for triple-negative breast cancer therapy.

Silencing STAT3 is confirmed as a promising therapeutic strategy for triple-negative breast cancer (TNBC) therapy to address the issue of its poor prognosis. In this study, the natural product cryptot...

Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity.

Triterpenoids are distributed widely in higher plants and are of interest because of their structural diversity and broad range of bioactivities. In particular, there is a very large literature on the...

Clinical Trials [3923 Associated Clinical Trials listed on BioPortfolio]

To Study And Compare Bioavailability And Safety Of Four Different Formulations Of The Study Drug

SB-742510 is a semi-synthetic pleuromutilin antibiotic that is being developed for treatment of respiratory infections. The purpose of this study is to estimate the bioavailability of fou...

Effect of Enamel Matrix Proteins on Clinical Attachment Level and Alveolar Bone in Periodontal Maintenance Patients

The purpose of the study is to determine the effect of enamel matrix protein derivative on an inflamed, periodontal-involved tooth. The hypothesis to be studied is that enamel matrix deriv...

Effect of Probiotic on Antibiotic-Associated Diarrhea

Diarrhea is a common side effect of antibiotics; it may prolong hospital stay, increase the risk of other infections, develop into more serious forms of disease, and lead to premature disc...

A Clinical Study of PHY906 as a Modulator of CPT-11 in Patients With Metastatic Colorectal Cancer

PHY906 is an oral form of a spray dried aqueous extract composed of four main herbs, which have been used in the Orient for nearly 2000 years for a variety of GI symptoms including diarrhe...

Semi-structured Chinese Medicine Treatment as an Adjuvant Therapy to the Management of Diabetic Nephropathy

This study aims to explore the effect of an adjuvant semi-individualized Chinese medicine treatment plan on type 2 diabetic patients with stages 2 to 3 chronic kidney disease and macroalbu...

Medical and Biotech [MESH] Definitions

A semi-synthetic antibiotic that is a chlorinated derivative of OXACILLIN.

Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.

A semi-synthetic cephalosporin antibiotic.

A semi-synthetic antibiotic related to penicillin.

A semi-synthetic aminoglycoside antibiotic that is used in the treatment of TUBERCULOSIS.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Epigenetics
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...


Searches Linking to this Article