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Progress in Nucleic Acid Research and... 1964
Review
Topics: Animals; Dactinomycin; In Vitro Techniques; Nucleic Acids
PubMed: 4157816
DOI: 10.1016/s0079-6603(08)60742-4 -
Postepy Higieny I Medycyny... 2005Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits high antibacterial and antitumor activity. Actinomycin D has been widely used in clinical... (Review)
Review
Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits high antibacterial and antitumor activity. Actinomycin D has been widely used in clinical practice since 1954 as an anticancer drug for treating many tumors and it is also a useful tool in biochemistry and molecular biology. According to the Internet bibliographic database -- MEDLINE, actinomycins, and mainly actinomycin D, have been the subject of about 3300 science papers so far, and this paper is a review of the information concerning the mechanisms of action of actinomycin D. There are several mechanisms of its action that are responsible for its cytotoxic and antitumor action, these being associated with DNA functionality, leading to RNA and, consequently, protein synthesis inhibition. The two main mechanisms are intercalation to DNA and the stabilization of cleavable complexes of topoisomerases I and II with DNA, in which a phenoxazone ring localizes between GpC base pair sequence in DNA and polypeptide lactones rings occupy a position in the minor groove of the DNA helix or the drug penetrates to a place in the DNA structure where topoisomerase binds with DNA, respectively. Moreover, the slow dissociation of actinomycin D from DNA complexes, its photodynamic activity and free radical formation, as well as other biochemical effects of activity of actinomycin D may be, as suggested, important factors that influence the biological activity of this drug. In the literature not enough convincing evidence has been proposed that could indicate one particular mechanism of action as responsible for the biological activity of actinomycin D.
Topics: Animals; Antibiotics, Antineoplastic; DNA; Dactinomycin; Humans
PubMed: 15995596
DOI: No ID Found -
Acta Chimica Slovenica Jun 2022DNA thermal denaturation was evaluated as a measure of the effect of antitumor drug actinomycin D on the stability of the double helix and also the effect of SDS...
DNA thermal denaturation was evaluated as a measure of the effect of antitumor drug actinomycin D on the stability of the double helix and also the effect of SDS micelles on actinomycin D - DNA complexes. The results indicated that the melting temperature of DNA was dependent on drug concentration, increasing with actinomycin D concentration. High thermal stabilization (about 10 °C) of the DNA helix after the association with actinomycin D clearly demonstrates the intercalative binding mode. The presence of SDS micelles leads to the release of intercalated actinomcyin D molecules from DNA double helix and their further relocation in surfactant micelles. These results highlighted that the drug release can be controlled in time and by varying the concentration and nature of surfactant.
Topics: DNA; Dactinomycin; Micelles; Surface-Active Agents; Temperature
PubMed: 35861079
DOI: 10.17344/acsi.2021.7189 -
Organic & Biomolecular Chemistry Feb 2023Three novel actinomycins, actimomycin S (1), neo-actinomycins C and D (2 and 3), and one new benzo[]oxazole alkaloid (4) were isolated from the sp. strain S22, along...
Three novel actinomycins, actimomycin S (1), neo-actinomycins C and D (2 and 3), and one new benzo[]oxazole alkaloid (4) were isolated from the sp. strain S22, along with three known congeners F (5), X (6) and X (7) and 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (8). The structures of the new products were elucidated by spectroscopic methods, and the absolute configuration of amino acid residues was determined by Marfey's analysis. Actinomycin S contains an aspartic acid (Asp) residue in the β-peptidolactone ring. This is the first report of an Asp residue within an actinomycin-type natural product. Notably, neo-actinomycins C and D feature a rare tetracyclic 5-oxazolo[4,5-]phenoxazine chromophore. Among these, neo-actinomycin D, with an unprecedented molecular formula, represents the highest molecular weight member in the actinomycin family. Actinomycins 1-3 exhibited antimicrobial activity against multiple resistant "ESKAPE" pathogens with MIC values ranging from 1.25 to 80.0 μg mL. In addition, 1-3 showed potent cytotoxic activities against the HepG2 liver carcinoma cell line with IC values of 0.10, 0.32, and 0.024 μM, respectively. Furthermore, 1 inhibited cell proliferation by inducing G0-G1 phase arrest in the cell cycle.
Topics: Dactinomycin; Streptomyces; Antineoplastic Agents; Spectrum Analysis; Amino Acids
PubMed: 36723156
DOI: 10.1039/d2ob02247h -
Scientific Reports Feb 2022Streptomycetes are major producers of bioactive natural products, including the majority of the naturally produced antibiotics. While much of the low-hanging fruit has...
Streptomycetes are major producers of bioactive natural products, including the majority of the naturally produced antibiotics. While much of the low-hanging fruit has been discovered, it is predicted that less than 5% of the chemical space of natural products has been mined. Here, we describe the discovery of the novel actinomycins L and L produced by Streptomyces sp. MBT27, via application of metabolic analysis and molecular networking. Actinomycins L and L are diastereomers, and the structure of actinomycin L was resolved using NMR and single crystal X-ray crystallography. Actinomycin L is formed via spirolinkage of anthranilamide to the 4-oxoproline moiety of actinomycin X prior to the condensation of the actinomycin halves. Such a structural feature has not previously been identified in naturally occurring actinomycins. Adding anthranilamide to cultures of the actinomycin X producer Streptomyces antibioticus, which has the same biosynthetic gene cluster as Streptomyces sp. MBT27, resulted in the production of actinomycin L. This supports a biosynthetic pathway whereby actinomycin L is produced from two distinct metabolic routes, namely those for actinomycin X and for anthranilamide. Actinomycins L and L showed significant antimicrobial activity against Gram-positive bacteria. Our work shows how new molecules can still be identified even in the oldest of natural product families.
Topics: Anti-Bacterial Agents; Biological Products; Biosynthetic Pathways; Dactinomycin; Gram-Positive Bacteria; Humans; Streptomyces antibioticus; Streptomycetaceae; ortho-Aminobenzoates
PubMed: 35181725
DOI: 10.1038/s41598-022-06736-0 -
Marine Drugs Dec 2021Actinomycins as clinical medicine have been extensively studied, while few investigations were conducted to discover the feasibility of actinomycins as antimicrobial...
Actinomycins as clinical medicine have been extensively studied, while few investigations were conducted to discover the feasibility of actinomycins as antimicrobial natural dye contributing to the medical value of the functional fabrics. This study was focused on the application of actinomycin X2 (Ac.X2), a peptide pigment cultured from marine-derived , in the dyeing and finishing of silk fabric. The dyeing potential of Ac.X2 with silk vs. cotton fabrics was assessed. As a result, the silk fabric exhibited greater uptake and color fastness with Ac.X2. Through Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analyses, some changes of chemical property for the dyed fabric and Ac.X2 were studied. The silk fabric dyed with Ac.X2 exhibited good UV protection ability. The antibacterial properties of dyed and finished silk were also evaluated, which exhibited over 90% antibacterial activity even after 20 washing cycles. In addition, the brine shrimp assay was conducted to evaluate the general toxicity of the tested fabric, and the results indicated that the dyed silk fabrics had a good biological safety property.
Topics: Animals; Anti-Bacterial Agents; Aquatic Organisms; Artemia; Coloring Agents; Dactinomycin; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Silk; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Streptomyces
PubMed: 35049871
DOI: 10.3390/md20010016 -
Postepy Higieny I Medycyny... 2005For over 60 years, actinomycins, well-known antibacterial and anticancer antibiotics, have been the subject of the scientific research. These compounds exhibit high... (Review)
Review
For over 60 years, actinomycins, well-known antibacterial and anticancer antibiotics, have been the subject of the scientific research. These compounds exhibit high toxicity and therefore are not widely used in the chemotherapeutic treatment of antibacterial and antifungal diseases. However, actinomycin D, the best-known compound from the actinomycin group, has been introduced into clinical practice as an anticancer drug. Actinomycin D, together with 7-amino-actinomycin D, also became a useful tool in biochemistry and molecular biology. The isolation, production, chemistry, and biological and clinical use of the actinomycins have been thoroughly investigated. Many derivatives of actinomycins, differing in chemical structure as well as biological activity, have been isolated and synthesized and their modifications involved not only the chromphoric phenoxazone ring, but also two cyclic pentapeptide lacton rings. Modifications of the actinomycins' chromophore mainly concerned introducing an amino group in position 2 and a carbon atom in position 7, but also modifications in positions 4, 6, and 8 of the phenoxazone ring. The actinomycin peptide moiety was mainly modified by replacement of amino acids in the pentapeptide rings and also by the synthesis of actinomycin derivatives with open peptide lacton rings. These modifications enabled separating the elements in the actinomycin structure which are responsible for the biological activity of these compounds. That was key information for recognizing the performance of these compounds, and an important way of planning effective new chemotherapeutics.
Topics: Animals; Antibiotics, Antineoplastic; Dactinomycin; Humans; Structure-Activity Relationship
PubMed: 15995594
DOI: No ID Found -
Nature Sep 1970
Topics: Dactinomycin; Lactones; Magnetic Resonance Spectroscopy; Models, Structural; Peptides
PubMed: 5452813
DOI: 10.1038/2271239a0 -
American Journal of Clinical Pathology Aug 1969
Topics: Animals; Antibiotics, Antineoplastic; Chemical Phenomena; Chemistry; Culture Techniques; DNA Replication; Dactinomycin; Humans; Models, Chemical; RNA
PubMed: 5798361
DOI: 10.1093/ajcp/52.2.130 -
Apoptosis : An International Journal on... Jun 2022Actinomycin D (ActD) was the first anticancer antibiotic approved for the management of human cancers. However, the notorious toxicity profile limits its widespread...
Actinomycin D (ActD) was the first anticancer antibiotic approved for the management of human cancers. However, the notorious toxicity profile limits its widespread application in cancers, including cancers of the aerodigestive tract. Recent studies show that combining low-dose ActD with existing chemotherapies could potentially protect normal cells from the toxicity of chemotherapy drugs through p53 activation (cyclotherapy). An understanding of ActD's effect on p53 signaling is critical for the meaningful application of ActD in cyclotherapy-based combinations. This study evaluated the anti-tumor efficacy and mechanism of action of ActD in aerodigestive tract cancers. We found that ActD strongly inhibited the growth of a panel of aerodigestive tract cancer cell lines and induced efficient apoptosis, although the sensitivity varies among cell lines. The IC values of ActD spanned between 0.021 and 2.96 nM. Mechanistic studies revealed that ActD increased the expression of total and phosphorylated p53 (ser15) in a time- and dose-dependent manner. Moreover, ActD-induced apoptosis is dependent on p53 in cells expressing wild-type p53 and that ActD induced context-dependent differential expression of downstream targets p21 and PUMA without significant effects on p27. In the final analysis, this study revealed that p53-p21 is the predominant pathway activated by low-dose ActD, supporting further development of ActD in cyclotherapy.
Topics: Antibiotics, Antineoplastic; Apoptosis; Dactinomycin; Humans; Neoplasms; Tumor Suppressor Protein p53
PubMed: 35267106
DOI: 10.1007/s10495-022-01720-5