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ABSTRACT
Introduction
The quinolone scaffold is a bicyclic benzene-pyridinic ring scaffold with nitrogen at the first position and a carbonyl group at the second or fourth position. It is endowed with a diverse spectrum of pharmacological activities, including antitumor activity, and has progressed into various development phases of clinical trials for their target-specific anticancer activity.
Areas covered
The present review covers both classes of quinolones, i.e. quinolin-2(H)-one and quinolin-4(H)-one as anticancer agents, along with their possible mode of binding. Furthermore, their structure-activity relationships, molecular mechanisms, and pharmacokinetic properties are also covered to provide insight into their structural requirements for their rational design as anticancer agents.
Expert opinion
Synthetic feasibility and ease of derivatization at multiple positions, has allowed medicinal chemists to explore quinolones and their chemical diversity to discover newer anticancer agents. The presence of both hydrogen bond donor (−NH) and acceptor (-C=O) functionality in the basic scaffold at two different positions, has broadened the research scope. In particular, substitution at the -NH functionality of the quinolone motif has provided ample space for suitable functionalization and appropriate substitution at the quinolone’s third, sixth, and seventh carbons, resulting in selective anticancer agents binding specifically with various drug targets.
Article highlights
The quinolone scaffold is of wide interest in medicinal chemistry, with various quinolone-based antibacterial drugs approved by FDA.
Quinolones have apparently exhibited excellent potency against various cancer cell lines.
Recently, several quinolone-based compounds have been patented, while four are under clinical development as anticancer agents.
Recent advances in the medicinal chemistry of quinolones based anticancer agents along with their SAR and biological studies have been compiled.
The SAR analysis have revealed the scope for optimization of the anticancer effect obtain efficient quinolone based anticancer agents in near future.
Abbreviations
| DNA | = | Deoxyribonucleic acid |
| EDG | = | Electron Donating Group |
| EGFR | = | Epidermal growth factor receptor |
| EWG | = | Electron Withdrawing Group |
| GI50 | = | Growth inhibitory power of a drug to inhibit 50% cell growth |
| HDAC | = | Histone deacetylase |
| IC50 | = | Concentration of drug at which 50% cell growth is inhibited |
| LD50 | = | Concentration of drug at which 50% cells die |
| MTT | = | (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) |
| NSCLC | = | Non small cell lung cancer |
| PBP | = | Penicillin Binding Protein |
| PD | = | Pharmacodynamics |
| PK | = | Pharmacokinetics |
| SAR | = | Structure activity relationship |
| Topo | = | Topoisomerase |
| Topo2β | = | Topoisomerase 2 beta |
| WHO | = | World Health Organization |
| FDA | = | Food & Drug Administration |
| PI3K | = | phosphoinositide-3-kinase–protein kinase |
| NSCLC | = | Non-Small Cell Lung Cancer |
| DPPH | = | 2,2-diphenyl-1-picrylhydrazyl |
| ATP | = | Adenosine triphosphate |
| ROS | = | Reactive oxygen species |
Declaration of interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.