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Cold Spring Harbor Protocols Apr 2018Radioactive reagents have been gradually replaced by nonisotopic reagents for some tasks in molecular biology. Concern over laboratory safety and the economic and...
Radioactive reagents have been gradually replaced by nonisotopic reagents for some tasks in molecular biology. Concern over laboratory safety and the economic and environmental aspects of radioactive waste disposal have been key factors in this change. Generally, the new nonisotopic systems have improved in terms of analytical sensitivity and the time required to obtain a result. The most prominent nonisotopic analytical methods exploit chemiluminescence, described here. This technique has been particularly effective when used in combination with an enzyme label, so that the amplifying properties of an enzyme label and the high sensitivity of a chemiluminescent detection reaction are combined to produce an ultrasensitive assay (e.g., chemiluminescent detection of peroxidase- and alkaline phosphatase-labeled proteins and nucleic acid probes). In all of the commonly used applications in molecular biology, the analytical performance of the chemiluminescent systems approaches that of I- or P-based systems. Chemiluminescent systems also avoid the lengthy signal detection times required with P-based methods, yielding results in minutes rather than days. In addition, chemiluminescent probes can be easily stripped from membranes, allowing the membranes to be reprobed many times without significant loss of resolution. Experimental protocols for directly attaching nonisotopic labels to nucleic acids and indirect labeling methods based on biotin, fluorescein, and digoxigenin labels are now well established. The ancillary reagents (e.g., avidin, streptavidin, antidigoxigenin, and antifluorescein enzyme conjugates) required for the indirect methods are widely available.
Topics: Acridines; Enzyme Assays; Immunoassay; Indicators and Reagents; Luminescent Measurements; Luminol
PubMed: 29610365
DOI: 10.1101/pdb.top098236 -
Mini Reviews in Medicinal Chemistry 2022Acridine derivatives have been thoroughly investigated and discovered to have multitarget qualities, inhibiting topoisomerase enzymes that regulate topological changes... (Review)
Review
UNLABELLED
Acridine derivatives have been thoroughly investigated and discovered to have multitarget qualities, inhibiting topoisomerase enzymes that regulate topological changes in DNA and interfering with DNA's vital biological function. This article discusses current progress in the realm of novel 9-substituted acridine heterocyclic compounds, including the structure and structure- activity connection of the most promising molecules. The IC values of the new compounds against several human cancer cell lines will also be presented in the publication. The review also looks into the inhibition of topoisomerase by polycyclic aromatic compounds.
BACKGROUND
Acridine rings can be found in molecules used in many different areas, including industry and medicine. Nowadays, acridines with anti-bacterial activity are of research interest due to decreasing bacterial resistance. Some acridine derivatives showed antimalarial or antiviral activity. Acridine derivatives were also investigated for anti-tumor activity due to the interaction with topoisomerase II and DNA base pairs. Considering these possible uses of acridine derivatives, this work overviewed all significant structure performances for the specific action of these compounds.
OBJECTIVE
The objective of this study is to review the activity of acridines as anti-proliferative agents.
METHODS
This review is designed as acridines acting as topoisomerase I and II inhibitors/ poison, Acridines on the G-quadraplux interaction, Acridines with metal complexes, Acridines with quinacrine scaffold, Acridines with sulphur moiety.
CONCLUSION
Although introduced in the 19 century, acridine derivatives are still of scientific interest. In this review, acridine derivatives with various biological activities (antiparasitic, antiviral, anti-bacterial, and antiproliferative) and their structure-activity relationship analyses are presented. Although several mechanisms of their action are known, the only important are discussed here. It can be concluded that the dominant mechanisms are DNA intercalation and interaction with enzymes.
Topics: Acridines; Antimalarials; Antineoplastic Agents; Antiviral Agents; Coordination Complexes; DNA; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Humans; Poisons; Quinacrine; Structure-Activity Relationship; Sulfur
PubMed: 35546777
DOI: 10.2174/1389557522666220511125744 -
The Alkaloids. Chemistry and Biology 2017There have been substantial developments in the chemistry and biology of the acridone alkaloids in the 16years since the topic was last reviewed in this series of... (Review)
Review
There have been substantial developments in the chemistry and biology of the acridone alkaloids in the 16years since the topic was last reviewed in this series of monographs (2000). The present survey covers the literature from mid-1999 to 2016. A brief overview of the biosynthesis of acridone alkaloids is followed by details of the occurrence and characterization of known alkaloids from new sources, and of novel alkaloids. The classes covered include simple acridone alkaloids, C-prenylacridones, furo[3,2-b]- and furo[2,3-c]acridones, pyrano[3,2-b]- and pyrano[2,3-c]acridones, and dimeric alkaloids containing acridone moieties. Syntheses of acridone alkaloids and certain analogs reported during the review period are comprehensively covered. The final section summarizes aspects of their bioactivity, including cytotoxicity and anticancer activity, antimicrobial and antiparasitic properties, and enzyme inhibition. The chapter concludes with a brief description of important bioactive synthetic analogs.
Topics: Acridones; Animals; Humans
PubMed: 28838426
DOI: 10.1016/bs.alkal.2017.06.001 -
The Alkaloids. Chemistry and Biology 2023The families of pyridoacridine, pyridoacridone, and pyrroloacridine alkaloids are fascinating classes of natural products that have attracted the attention of chemists... (Review)
Review
The families of pyridoacridine, pyridoacridone, and pyrroloacridine alkaloids are fascinating classes of natural products that have attracted the attention of chemists for over 80 years. Since the first purification of a brightly colored molecule isolated from the sea anemone Calliactis parasitica in 1940, over 110 examples of these alkaloids have been reported from marine organisms. While the paucity of numbers of protons relative to carbons and nitrogens in these molecules presents challenges in structure solution, the chemist is rewarded by their bright pigmented colors and typically diverse biological activities. In the past, several authors have proposed biosynthetic relationships within the pyridoacridine family of alkaloids, formulating a family tree derived from the reaction of dopaminequinone and kynuramine to tie together over 75 alkaloids. Inclusion of two additional quinones, and one homologous diamine, building blocks, for which there is biomimetic synthesis support, is suggestive of a more expansive connected biogenesis that encompasses not only pyridoacridines, but also pyridoacridone, and pyrroloacridine alkaloids. This review covers the isolation, structure elucidation, and proposed biosynthesis and biogenesis of pyridoacridine, pyridoacridone and pyrroloacridine marine alkaloids published to the end of 2022. Biomimetic or bio-inspired syntheses of the compound classes are described and new biological activities reported since 2004 are updated.
Topics: Acridines; Alkaloids; Biological Products; Biomimetics
PubMed: 37716797
DOI: 10.1016/bs.alkal.2023.06.001 -
Biomedicine & Pharmacotherapy =... Feb 2022Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and... (Review)
Review
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
Topics: Acridines; Alzheimer Disease; Butyrylcholinesterase; Cholinesterase Inhibitors; Humans; Methoxsalen; Structure-Activity Relationship
PubMed: 34953393
DOI: 10.1016/j.biopha.2021.112556 -
Pharmacological Research Feb 2017Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro... (Review)
Review
Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
Topics: Alzheimer Disease; Animals; Anticholinergic Syndrome; Cholinesterase Inhibitors; Humans; Tacrine; United States; United States Food and Drug Administration
PubMed: 28040533
DOI: 10.1016/j.phrs.2016.12.033 -
Journal of Applied Toxicology : JAT Jan 2020Proflavine derivatives are extremely interesting chemotherapeutic agents, which have shown promising pharmaceutical potential due to their wide range of biological... (Review)
Review
Proflavine derivatives are extremely interesting chemotherapeutic agents, which have shown promising pharmaceutical potential due to their wide range of biological activities. This review summarizes the current state of research into the anticancer, antimicrobial, antimalarial and antileishmanial properties of these attractive compounds. Our attention has focused on new classes of proflavine conjugates, which display significant levels of anticancer activity. Highly promising cytotoxic properties have been identified in proflavine conjugates with imidazolidinones, ureas and thioureas. In particular, proflavine-dialkyldithioureas displayed substantial cytotoxic effect against the human leukemia HL-60 cells with IC values from 7.2 to 34.0 μm. As well, palladium complexes with proflavine ligand have important biologic activity. The LC values of these complexes were significantly lower than that of cisplatin against the SK-BR-3 cell line.
Topics: Acriflavine; Animals; Anti-Infective Agents; Antineoplastic Agents; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Molecular Structure; Proflavine; Structure-Activity Relationship
PubMed: 31222780
DOI: 10.1002/jat.3818 -
Cytometry. Part a : the Journal of the... Jun 2020Briefly depicted are the publications in CYTOMETRY that received the highest frequency of citations. Among them are seminal papers describing application of...
Briefly depicted are the publications in CYTOMETRY that received the highest frequency of citations. Among them are seminal papers describing application of metachromatic fluorochrome acridine orange to differentially stain DNA versus RNA or to analyze susceptibility of DNA in situ to denaturation; both features being markers of different sections of the cell cycle including identification of noncycling quiescent cells. The papers reviewing detection of cyclins D1, E, A or B1, each in relation to cell cycle phase, were also among the highly cited ones. The highest citation rates received publications describing development of the TUNEL methodology to detect apoptotic DNA fragmentation, and more recently expression of ϒH2AX to reveal DNA damage. © 2020 International Society for Advancement of Cytometry.
Topics: Acridine Orange; Cell Cycle; DNA; Flow Cytometry; Fluorescent Dyes
PubMed: 32511890
DOI: 10.1002/cyto.a.24043 -
Journal of Applied Toxicology : JAT Oct 2017Acridines possess two characteristics that have led many researchers to consider the agents interesting targets for future development as potential farmacophores: the... (Review)
Review
Acridines possess two characteristics that have led many researchers to consider the agents interesting targets for future development as potential farmacophores: the planar acridine skeleton, which is able to intercalate into DNA, and the intense fluorescence of the agents. This review offers a study of the multifunctional character of acridines and the synthesis of novel acridine derivatives, with particular focus being placed on isothiocyanates and their congeners, e.g. thioureas, isothioureas, quaternary ammonium salts and platinum/gold conjugates. The review provides an overview of the structure, spectral properties, DNA binding and biological activity of acridinylthiourea congeners. These acridinylthiourea derivatives display significant cytotoxic activities against different types of cancer cell lines at micromolar concentrations. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Acridines; Antineoplastic Agents; Cell Line, Tumor; DNA Damage; Humans; Isothiocyanates; Proflavine; Structure-Activity Relationship; Thiourea
PubMed: 28370171
DOI: 10.1002/jat.3464 -
Current Topics in Medicinal Chemistry 2021Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy... (Review)
Review
Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance, especially multidrug resistance, remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan, 2015 to Feb, 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for a further rational design of novel anticancer agents.
Topics: Acridines; Antineoplastic Agents; Apoptosis; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Molecular Structure
PubMed: 34348622
DOI: 10.2174/1568026621666210804115203