Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Abstract

Abstract: This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.

Keywords: Antibiotics; Antitumor agents; Antiviral activity; Conjugates; Drug research; Hybrid drugs.

Fig. 1

General structure of fluoroquinolones with atom numeration

Fig. 2

Structures of flumequine–Cu(II)-2,2′-bipyridylamine (1), sparfloxacin–Cu(I)-2,2′-biquinoline (2), sparfloxacin–Cu(II)-2,2′-bipyridine (3), sparfloxacin–Cu(II)-1,10-phenanthroline (4), moxifloxacin–Cu(II)-bipyridyl (5), and gatifloxacin–Cu(II)–bipyridyl (6) complexes

Fig. 3

Structures of polyphosphazene–fluoroquinolone polymers. R¹ = Et for norfloxacin and cyclopropyl for ciprofloxacin, R² = H, Me, Bn for glycine, alanine, or phenylalanine, respectively

Fig. 4

Structure of peptide–quinolone conjugate 14

Fig. 5

Structure of peptide M33-levofloxacin hybrid 17

Fig. 6

Structures of fluoroquinolone-β-octaarginine conjugates 19a, 19b

Fig. 7

Structures of siderophore and fluoroquinolone hybrids 27

Fig. 8

Structures of catecholate–ciprofloxacin conjugates 30a–30e

Fig. 9

Structures of fluoroquinolone–siderophore hybrids 31a–31k

Fig. 10

Structures of fluoroquinolone conjugates 41, 42

Fig. 11

Structures of triazole–fluoroquinolone hybrids 45

Fig. 12

Structures of fluoroquinolone–triazole hybrids 51–53

Fig. 13

Structure of rifamycin–quinolone conjugate 54 (CBR-2029)

Fig. 14

Structure of cadazolid

Fig. 15

Structures of tobramycin–fluoroquinolone conjugates 57–59

Fig. 16

Structures of ciprofloxacin–neomycin B hybrids 60

Fig. 17

Structure of quinolone–pyrazinamide hybrid 64

Fig. 18

Structures of dihydroartemisinin–fluoroquinolone conjugates 65–67

Fig. 19

Structures of miconazole-based ciprofloxacin conjugates 71

Fig. 20

Structures of ciprofloxacin dimers 77–84

Fig. 21

Structures of flavonoid–fluoroquinolone hybrids 97–98

Fig. 22

Structure of fluoroquinolone and anilinouracil hybrid 99 (251D)

Fig. 23

Structure of 3-arylfuran-2(5H)-one-fluoroquinolone conjugates 100

Fig. 24

Structure of fluoroquinolone–chalcone hybrids 101

Fig. 25

Structure of desfluoroquinolones 104a, 104b

Fig. 26

Structures of desfluoroquinolones 105a–105c

Fig. 27

Structure of compounds 109a–109d