Antimicrobial Activity of Naphthyridine Derivatives

Abstract

To combat the problem of the increasing drug resistance of microorganisms, it is necessary to constantly search for new medicinal substances that will demonstrate more effective mechanisms of action with a limited number of side effects. Naphthyridines are N-heterocyclic compounds containing a fused system of two pyridine rings, occurring in the form of six structural isomers with different positions of nitrogen atoms, which exhibit a wide spectrum of pharmacological activity, in particular antimicrobial properties. This review presents most of the literature data about the synthetic and natural naphthyridine derivatives that have been reported to possess antimicrobial activity.

Keywords: antimicrobial activity; nalidixic acid; naphthyridine derivatives; structure–activity relationships.

Figure 1

Naphthyridine isomers.

Figure 2

Nalidixic acid and its derivatives used in medicine.

Figure 3

Nalidixic acid derivatives 9–10.

Figure 4

1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid derivatives.

Figure 5

1-(2,4-Difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid derivatives 12a–e.

Figure 6

Structures of derivatives 13a–c.

Figure 7

Nalidixic acid-D-(+)-glucosamine conjugate 14.

Figure 8

Nalidixic acid-based 1,2,4-triazole derivatives 15–18.

Figure 9

Structures of 1,8-naphthyridine-3-carboxylic acid amides 19.

Figure 10

Nalidixic acid derivatives with a 6-nitro group, 20a–g.

Figure 11

Nalidixic acid hydrazide derivative and its metal complexes, 21a–d.

Figure 12

7-[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]-1-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid 22.

Figure 13

Antibacterial 1,8-naphthyridine derivatives 23–25.

Figure 14

Hydrazono and azo derivatives of 1,8-naphthyridine 26–29.

Figure 15

1,8-Naphthyridines with oxadiazole and phenyl ring 30a–d.

Figure 16

1,8-Naphthyridinones 31a–m.

Figure 17

2-(β-D-galactopyranosylmethyl)-1,8-naphthyridine 32.

Figure 18

Polymers 33a–b.

Figure 19

1,8-Naphthyridine derivatives 34–35.

Figure 20

Antimalarial 2-oxo-tetrahydro-1,8-naphthyridine derivatives 36–37.

Figure 21

3-Cyano-2-ethoxy-4-phenyl-7-substituted-1,8-naphthyridines 38a–b.

Figure 22

6-Aryl-1,8-naphthyridine-2-carbonitrile derivatives 39–40.

Figure 23

2-Cyclopropyl-1,8-naphthyridine derivatives with antibacterial activity.

Figure 24

Thiosemicarbazides and 1,3,4-oxadiazoles of 1,8-naphthyridine 44–45.

Figure 25

N-benzylidene-N′-(5-methyl-2-acetamido[1,8]naphthyridin-7-yl)hydrazine derivatives 46.

Figure 26

3-(2-Methyl-1,8-naphthyridin-3-yl)ureas 47.

Figure 27

1-Benzyl-N-cyclohexyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide 48.

Figure 28

Benzo[b][1,8]naphthyridine derivatives 49a–j.

Figure 29

4-Amino-2-phenyl-5,7-di(thien-2-yl)-1,8-naphthyridine-3-carbonitrile 50.

Figure 30

1,8-Naphthyridine sulphonamides 51a–d.

Figure 31

2-Chloro-1,8-naphthyridine-3-carbaldyhyde 52.

Figure 32

Naphthyridin-2-one derivatives 53 as FabI and FabK inhibitors.

Figure 33

4-Amino-6-benzotriazol-1-yl-1,2-dihydro-5-methyl-2-oxo-1,8-naphthyridine-3-carbonitrile 54.

Figure 34

4,7-Diamino-2-oxo/thioxo-1,2-dihydro[1,8]naphthyridine-3,6-dicarbonitrile, 55.

Figure 35

Imidazo [1,2-a][1,8]naphthyridine derivatives 56–57.

Figure 36

N-3-diaryl-1,8-naphthyridin-2-amine derivatives 58a–c.

Figure 37

9-(3-Fluoro-4-methoxyphenyl)-6-aryl-[1,2,4]triazolo [4,3-a][1,8]naphthyridine derivatives 59a–c.

Figure 38

4-Aryl-2-(3-(2-(trifuoromethyl)phenyl)-1,8-naphthyridin-2-yl)phthalazin-1(2H)-ones 60a–h.

Figure 39

2-(2-(3-Nitrophenyl)-1,8-naphthyridin-3-yl)-5-phenyl-1,3,4-oxadiazoles derivatives 61a–h.

Figure 40

2-Bromo-N-(3-aryl-1,8-naphthyridin-2-yl)thiazole-4-carboxamide derivatives 62a–f.

Figure 41

N-(3-aryl-1,8-naphthyridin-2-yl)-5-(2-methyl-1,8-naphthyridin-3-yl)thiazol-2-amine derivatives 63a–e.

Figure 42

5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amines 64a–k.

Figure 43

2-Methoxy-3-aryl-1,8-naphthyridine derivatives 65a–j.

Figure 44

2-Oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylates 66a–k.

Figure 45

3-Iodo-1,8-naphthyridine derivatives 67a–g.

Figure 46

2-{4-[(3-Aryl-1,8-naphthyridin-2-yl)amino]-phenyl}-1H-benzo[de]isoquinoline-1,3(2H)-diones 68a–h.

Figure 47

6-(2-Chloro-4-fluorophenyl)-9-phenylimidazo[1,2-a][1,8]naphthyridines 69a–h.

Figure 48

Silver(I) complexes with 1,8 naphthyridine 70a–b.

Figure 49

3-Chloro-1-((3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)amino)azetidin-2-ones 71a–j.

Figure 50

N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide 72.

Figure 51

1,8-Naphthyridine derivatives 73.

Figure 52

2-Aryl-1,8-naphthyridine derivatives 74a–c.

Figure 53

Fused naphthyridines 75–78.

Figure 54

Naphtho[2,3-b][1,8]naphthyridine derivatives 79–81.

Figure 55

Chromeno-1,8-naphthyridine derivatives 82a–l.

Figure 56

Ketolides containing naphthyridine scaffold, 83a–b.

Figure 57

6{D(-)-a(4-hydroxyl-1,5-naphthyridine-3-carboxamido)phenylacetamido} sodium penicillinate 84.

Figure 58

N-{[8-(4-tert-butylphenyl)-1,5-naphthyridin-4-yl]methyl}guanidine 85.

Figure 59

2-(3-Fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethane-1,2-diol derivatives 86a–b.

Figure 60

3-Fluoro-6-methoxy-1,5-naphthyridine derivatives 87a–b.

Figure 61

2-[2-(3-Fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl]-1,3-dioxan-5-amine derivatives 88.

Figure 62

Pyronaridine 89.

Figure 63

Chromeno [4,3-b]naphthyridines and quinolino [4,3-b]naphthyridines 90–91.

Figure 64

Silver(I) complexes with 1,5-naphthyridines 92a–c.

Figure 65

Canthin-6-one 93a and 10-methoxycanthin-6-one 93b.

Figure 66

Aaptamine 94a and 1,4-dibenzylaaptamine 94b.

Figure 67

Silver(I) and gold(III) coordination compounds with 1,6-naphthyridine scaffold.

Figure 68

7-Amino-3-[(6-hydroxy-4,7-dimethoxy-1-benzofuran-5-yl)carbonyl]-5-oxo-5,6-dihydro-1,6-naphthyridine-8-carbonitrile 97.

Figure 69

8-Hydroxy-1,6-naphthyridine derivatives 98–99.

Figure 70

Benzo[h][1,2,4]triazolo[3,4-a][2,6]naphthyridine derivatives 100a–d.

Figure 71

Calycanthine 101.

Figure 72

Isoquino[1,2-a][2,7]naphthyridine derivatives 102a–g.

Figure 73

8-(3,4,5-Trimethoxyphenyl)-5,6,6a,7,8,9,10,10a–octahydropyrimido[4,5-c][2,7]naphthyridine -1,3-diamine 103.

Figure 74

2,7-Naphthyridine-4-carbonitrile derivatives 104 and thieno [2,3-c][2,7]naphthyridine derivatives 105.

Figure 75

Eupolauridine and its derivatives, 106–107.

Figure 76

Pyrido[2,3,4-kl]acridin-6-one derivatives 108–110.

Figure 77

Eupomatidines 111a–c, imbiline 112a, and hadranthine A 112b.

Figure 78

Sampangines 113a–b and diplamines 114a–b.

Figure 79

Amphimedine analogues 115–117.

Figure 80

Ascididemines 118–119.