Nonclassical Biological Activities of Quinolone Derivatives

Abstract

Quinolones are considered as a big family of multi-faceted drugs; their chemical synthesis is flexible and can be easily adapted to prepare new congeners with rationally devised structures. This is shown by the description of many thousands of derivatives in the literature. Scientists could accurately describe their QSAR, which is essential for effective drug design. This also gave them the chance to discover new and unprecedented activities, which makes quinolones an endless source of hope and enables further development of new clinically useful drugs.Quinolones are among the most common frameworks present in the bioactive molecules that have dominated the market for more than four decades. Since 1962, 4(1H)-quinolone-3-carboxylic acid derivatives are widely used as antibacterial agents. Quinolones have a broad and potent spectrum of activity and are also used as second-line drugs to treat tuberculosis (TB). Recently, quinolones have been reported to display "nonclassical" biological activities, such as antitumor, anti-HIV-1 integrase, anti-HCV-NS3 helicase and -NS5B-polymerase activities.The present review focuses on the structural modifications responsible for the transformation of an antibacterial into an anticancer agent and/or an antiviral agent. Indeed, quinolones' antimicrobial action is distinguishable among antibacterial agents, because they target different type II topoisomerase enzymes. Many derivatives of this family show high activity against bacterial topoisomerases and eukaryotic topoisomerases, and are also toxic to cultured mammalian cells and in vivo tumor models. Moreover, quinolones have shown antiviral activity against HIV and HCV viruses. In this context the quinolones family of drugs seem to link three different biological activities (antibacterial, anticancer, and the antiviral profiles) and the review will also provide an insight into the different mechanisms responsible for these activities among different species.

Modulation of HIV-1-Induced Activation of Plasmacytoid Dendritic Cells by 6-Desfluoroquinolones

“…However, different biological activities have been reported during the years for the quinolone ''privileged-structure.'' [15][16][17] Both CQ and certain quinolone derivatives have been described as exerting inhibitory activity on HIV replication in vitro. 16,18,19 CQ can prevent HIV-dependent pDC activation by interfering with endosomal acidification and HIV trafficking into the TLR7/ 9-bearing endosomes.…”

Antibacterial and Urease Inhibitory activity of New Piperazinyl N-4 Functionalized Ciprofloxacin-oxadiazoles

“…Compounds 5a-f were characterized by a singlet signal (2H) at  ~3.97 ppm representing CH 2 of the bridge between ciprofloxacin and oxadiazole moiety in 1 H-NMR-spectra. Additionally, compounds 5c was characterized by a singlet signal (3H) at  2.41 ppm assigned to p-CH 3 group, while compound 5d revealed a similar singlet signal at  3.84 ppm due to p-OCH 3 protons, 13 C-NMR Spectra of compounds 5a-f were charecterized by a signal at  ~52.50 assigned to CH 2 of the bridge between piperazine ring and oxadiazole scaffold. Compounds 5c was also characterized by an additional aliphatic signal at  21.77 ppm related to p-CH 3 , however, compound 5d showed a p-OCH 3 signal at  55.58 ppm.…”

“…Quinolones had emerged as interesting synthetic compounds with diverse chemical structures and biological activities. [1][2][3] They primary appeared as antibacterial agents with considerable impact in management of different infectious diseases. [4,5] Therefore, quinolones attracted researchers to design more derivatives, leading to various members of this class are widely used as drugs nowadays.…”

Recent updates of fluoroquinolones as antibacterial agents

“…Placement of an aminopyrrolidine can improve Gram‐positive activity, whereas a piperazine generally enhances potency against Pseudomonas . Alkylation of the five‐membered or six‐membered heterocycle (pyrrolidines or piperazines) also enhances activity against Gram‐positive bacteria …”

“…Fluoroquinolones represent one of the most common drugs used nowadays in treatment of various bacterial infections including urinary tract, upper and lower respiratory tract, skin, bone, soft tissue infections as well as community acquired pneumonia . Besides their typical antibacterial activity, fluoroquinolones also displayed diverse atypical biological profiles such as anti‐tumor, anti‐tubercular, anti‐HIV, anti‐malarial, and anti‐Alzheimer activities …”