The potential of acridines (amsacrine) as a topoisomerase II inhibitor or poison was first discovered in 1984, and since then, a considerable number of acridine derivatives have been tested as topoisomerase inhibitors/poisons, containing different substituents on the acridine chromophore. This review will discuss a series of studies published over the course of the last decade, which have investigated various novel acridine derivatives against topoisomerase II activity.
Heterocycles have long been the focus of intensive study in attempts to develop novel therapeutic compounds, and acridine, a polynuclear nitrogen molecule containing a heterocycle, has attracted a considerable amount of scientific attention. Acridine derivatives have been studied in detail and have been found to possess multitarget properties, which inhibit topoisomerase enzymes that regulate topological changes in DNA and interfere with the essential biological function of DNA. This article describes some recent advancements in the field of new 9-substituted acridine heterocyclic agents and describes both the structure and the structure-activity relationship of the most promising molecules. The article will also present the IC50 values of the novel derivatives against various human cancer cell lines. The mini review also investigates the topoisomerase inhibition and antibacterial and antimalarial activity of these polycyclic aromatic derivatives.
- MeSH
- akridiny chemie farmakologie toxicita MeSH
- antibakteriální látky chemie farmakologie toxicita MeSH
- antimalarika chemie farmakologie toxicita MeSH
- inhibitory topoisomerasy II chemie farmakologie toxicita MeSH
- lidé MeSH
- nádorové buňky kultivované účinky léků MeSH
- protinádorové látky chemie farmakologie toxicita MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
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.
- MeSH
- akridiny chemická syntéza farmakologie MeSH
- isothiokyanatany chemická syntéza farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- poškození DNA účinky léků MeSH
- proflavin chemická syntéza farmakologie MeSH
- protinádorové látky chemická syntéza farmakologie MeSH
- thiomočovina chemická syntéza farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
