Hydrazide-hydrazones as potential antimicrobial agents: overview of the literature since 2010

Abstract

Hydrazide-hydrazone derivatives are present in many bioactive molecules and display a wide variety of biological activities, such as antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antiviral, and antiprotozoal action. Therefore, many medicinal chemists synthesize various hydrazide-hydrazones and evaluate them for biological activities. Among biological properties of this class of compounds, antimicrobial activity is the most frequently encountered in scientific literature. This paper is focused on the overview of the literature findings of the last six years (2010-2016) covering the research on antimicrobial activity of hydrazide-hydrazone derivatives. This review may also serve as a useful guide for the development of new hydrazide-hydrazones as potential antimicrobial agents.

Keywords: Antibacterial activity; Antifungal activity; Antitubercular activity; Hydrazide–hydrazone; MIC.

Fig. 1

Chemical structures of medicines containing hydrazide–hydrazone moiety: nitrofurazone (a), furazolidone (b) and nitrofurantoin (c)

Fig. 2

Benzimidazoles showing interesting activity against Salmonella typhimurium. R = Cl (1); Br (2)

Fig. 3

New derivatives of cholic acid with hydrazide–hydrazone moiety. R = 4-ClC₆H₄ (3); 4-BrC₆H₄ (4); 4-NO₂C₆H₄ (5); 3-ClC₆H₄ (6); 4-Cl-3-NO₂C₆H₃ (7)

Fig. 4

Hydrazide–hydrazones of 4-chlorophenylsulfonyl acid with antibacterial activity. R = 3-OCH₃-C₆H₄ (8); 3-OH-C₆H₄ (9); 4-OH-3-OCH₃-C₆H₃ (10)

Fig. 5

Isonicotinoyl hydrazide analog with significant activity against S. aureus

Fig. 6

Indoles containing hydrazide–hydrazone moiety

Fig. 7

New 3-ethoxy-4-hydroxybenzylidene/4-nitrobenzylidene hydrazide–hydrazones with significant antibacterial activity

Fig. 8

1,2-Dihydropyrimidine derivatives with antibacterial activity

Fig. 9

Novel hydrazide–hydrazones obtained from 4-aminobenzoic acid hydrazide. R = Br (23); Cl (24); OCH₃ (25)

Fig. 10

Methylthiadiazoles with significant activity against Bacillus subtilis. R = F (26); Br (27)

Fig. 11

New imidazole derivatives containing hydrazide–hydrazone moiety

Fig. 12

New derivatives of 2,5-difluorobenzoic acid with hydrazide–hydrazone moiety. R = 4-CF₃ (30); 2-CF₃ (31); 2,4-diF (32)

Fig. 13

Novel hydrazide–hydrazones of nicotinic acid

Fig. 14

Novel hydrazide–hydrazone derivatives of 4-(4-chlorophenyl)cyclohexanecarboxylic acid as potential antibacterial agents. R = 2,4-diF-C₆H₃ (35); 2,6-diF-C₆H₃ (36); 3,4-diF-C₆H₃ (37)

Fig. 15

2-(2,3-Dihydrobenzofuran-5-yl)acetic acid derivatives with interesting antibacterial properties

Fig. 16

New anacardic acid hydrazide derivatives. R = 3,4-diOCH₃ (40); 3,4,5-triOCH₃ (41); 4-SO₂CH₃ (42)

Fig. 17

Novel pefloxacin derivatives with interesting antibacterial activity. R = 2,6-diCl (43); 4-NO₂ (44); 3,4,5-triOCH₃ (45); 5-Br-2-OH (46); 2,5-diOCH₃ (47); 3-OH (48)

Fig. 18

N-substituted-1-benzyl-1H-1,2,3-triazole-carbohydrazide derivatives with potential antibacterial activity

Fig. 19

Benzohydrazide derivatives with interesting antibacterial activity. R = OH (53); 3,4,5-triOCH₃ (54)

Fig. 20

Hydrazide–hydrazones with interesting antitubercular activity

Fig. 21

New 5-nitro-2-furoic acid hydrazide derivatives with potent in vitro antitubercular activity

Fig. 22

Novel thioureas with activity against Mycobacterium tuberculosis H37Rv

Fig. 23

Hydrazide–hydrazone obtained from isonicotinic hydrazide with in vitro activity against M. tuberculosis isoniazid-susceptible strain

Fig. 24

Indole derivatives containing hydrazide–hydrazone scaffold with antitubercular activity. R = H (77); CH₃ (78); C₂H₅ (79); C₃H₇ (80); C₆H₅ (81)

Fig. 25

Novel indole derivatives with significant antitubercular activity. 82: R ₁ = COOH, R ₂ = H; 83: R ₁ = COOC₂H₅, R ₂ = H; 84: R ₁ = COOC₂H₅, R ₂ = Cl; 85: R ₁ = COOC₂H₅, R ₂ = CH₃

Fig. 26

Pyrrolidinones with hydrazone moieties with antifungal activity. R=N(CH₃)₂ (86); Cl (87)

Fig. 27

Hydrazide–hydrazones with significant antifungal activity against Candida tenuis and Aspergillus niger. R=N(CH₃)₂ (88); Cl (89)

Fig. 28

Hydrazide–hydrazones of benzoic acid with antifungal activity. R = H (90); CH₃ (91); OCH₃ (92); Cl (93)

Fig. 29

Hydrazide–hydrazones of 4-nitrobenzoic acid with the antifungal activity. R = H (94); CH₃ (95)

Fig. 30

Hydrazide–hydrazone derivatives of 4-hydroxybenzoic acid with activity against Candida glabrata. R = H (96); CH₃ (97)