A “Double-Edged” Scaffold: Antitumor Power within the Antibacterial Quinolone
نویسندگان
چکیده
In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today's predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents.
منابع مشابه
A Mini Review on the Study of New Broad-Spectrum Antimicrobial Fluoroquinolone JNJ-Q2
The prokaryotic type II topoisomerases (DNA gyrase and topoisomerase IV) and the eukaryotic type II topoisomerases represent the cellular targets for quinolone antibacterial and anticancer agents. Both enzymes effort the selectively shift from an antibacterial to an antitumor activity. In the search for potential molecule in the quinolones series, some of quinolone analogs displayed antibacteri...
متن کاملSynthesis of new piperazinyl quinolones and investigation of their in vitro antibacterial activities
Quinolone antibacterial agents are currently used for the treatment of various bacterial infections. The nature of functional group at the 7 position of the quinolone ring system is known to have strong influence on the spectrum and extent of in vitro antibacterial activity. Accordingly, a series of N-L2- oxo-2-(2- furyl) and N-[2- oxyimino (2- furyl) ethyl] piperazinyl quinolone derivatives...
متن کاملEvaluation of antibacterial activity of new N-piperazinyl quinolone derivatives with 1,3,4.thiadiazole group
quinolones are broad-spectrum antibacterial agents.they have many clinical uses which are increasing.quinolones exert antibacterial activity primarily by inhibiting bacterial DNA gyrase.the inhibition of DNA gyrase by the quinolones are greatly influenced by the nature of the C-7 substituent on the quinolones molecule.substitution of bulky functional groupd is also possible in C-7 position.furt...
متن کاملSynthesis and Antimicrobial Activity of some Tetrahydro Quinolone Diones and Pyrano[2,3-d]pyrimidine Derivatives
There has been special interest in the chemistry of quinolone and pyrimidine derivatives due to their diverse biological activities such as anticonvulsant, anti-malarial agents, antibacterial, antiviral, cytostatic, antithelemintic, antigenotoxic, anti-cancer agents. These compounds are also used as targeting delayed-type hypersensivity and anti-convulsant agents. As a part of our research work...
متن کامل