Acylhydrazones and Their Biological Activity: A Review

Abstract

Due to the structure of acylhydrazones both by the pharmacophore -CO-NH-N= group and by the different substituents present in the molecules of compounds of this class, various pharmacological activities were reported, including antitumor, antimicrobial, antiviral, antiparasitic, anti-inflammatory, immunomodulatory, antiedematous, antiglaucomatous, antidiabetic, antioxidant, and actions on the central nervous system and on the cardiovascular system. This fragment is found in the structure of several drugs used in the therapy of some diseases that are at the top of public health problems, like microbial infections and cardiovascular diseases. Moreover, the acylhydrazone moiety is present in the structure of some compounds with possible applications in the treatment of other different pathologies, such as schizophrenia, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Considering these aspects, we consider that a study of the literature data regarding the structural and biological properties of these compounds is useful.

Keywords: acylhydrazone; anti-inflammatory; antimicrobial; antioxidant; antiparasitic; antiviral; cytotoxic; intermediates; properties; synthesis.

Figure 1

Structures of some representative bioactive molecules bearing the acylhydrazone template.

Figure 2

Isomers of acylhydrazone derivatives.

Figure 3

Intramolecular hydrogen bond.

Scheme 1

General synthesis reaction of acylhydrazones.

Figure 4

Structure of 5-bromo-1-methyl-N’-[(E)-(1-methyl-1H-indol-3-yl)methylidene]-1H-indole-3-carbohydrazide 5 with antitumor action.

Figure 5

Structure of (E)-1-(4-methoxybenzyl)-N’-(7-methyl-2-oxoindolin-3-ylidene)-1H-1,2,3-triazole-4-carbohydrazide 6 with antiproliferative action.

Figure 6

Structures of N’-(1-(4,7-dihydroxy-2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide 7a and N’-(1-(4-hydroxy-2-oxo)-2H-chromen-3-yl)ethylidene)benzohydrazide 7b with cytotoxic action.

Figure 7

Structures of acridine-benzohydrazides 8a–d with anticancer activity.

Figure 8

Structure of compound 9 showing antitumor action.

Figure 9

Structure of azo-hydrazone analog 10 with antiproliferative activity.

Figure 10

Structure of derivative 11 with antiproliferative action.

Figure 11

Structures of indole-hydrazone derivatives 12a–c with antiproliferative and antioxidant actions.

Figure 12

Structure of acylhydrazone 13 with antitumor action.

Figure 13

Structures of the acylhydrazone class compounds 14a–d with cytotoxic effect.

Figure 14

Structures of acylhydrazones 15–17 with cytotoxic action.

Figure 15

Structure of the acylhydrazone derivative 18 with cytotoxic action.

Figure 16

Structures of compounds 19 and 20 with cytotoxic action.

Figure 17

Structure of acylhydrazone derivative 21 with antitumor action.

Figure 18

Structures of acylhydrazones 22a–c with cytotoxic action.

Figure 19

Structure of compound 23 with intense antitumor action.

Figure 20

Structure of the acylhydrazone derivative 24 with antitumor action.

Figure 21

Structures of acylhydrazone compounds 25a,b with antitumor effect.

Figure 22

Structure of acylhydrazone 26 with antitumor action.

Figure 23

Structure of compound 27 with antitumor activity.

Figure 24

Structure of compound 28 with lactate dehydrogenase A inhibitory action.

Figure 25

Structures of the salts of acylhydrazones 29a,b with antimicrobial action.

Figure 26

Structure of acylhydrazone 30 with tuberculostatic action.

Figure 27

Structures of acylhydrazones 31a–g with antibacterial and antifungal actions.

Figure 28

Structures of acylhydrazones 32a–d with antibacterial action.

Figure 29

Structures of acylhydrazone derivatives 33a,b and 34a–c with antibacterial action.

Figure 30

Structures of acylhydrazone derivatives 35a–d with antimicrobial action.

Figure 31

Structures of acylhydrazones 36a–d with antibacterial action.

Figure 32

Structures of derivatives 37a,b with antibacterial action.

Figure 33

Structure of acylhydrazone 38 with antimicrobial action.

Figure 34

Structures of acylhydrazones 39 and 40 with antimicrobial action.

Figure 35

Structures of acylhydrazones 41a–f with antibacterial and cytotoxic actions.

Figure 36

Structure of acylhydrazone 42 with antimicrobial action.

Figure 37

Structures of acylhydrazones 43a–h screened for antibacterial activity.

Figure 38

Structures of acylhydrazone derivatives 44a–e and 45a,b with antifungal action.

Figure 39

Structures of acylhydrazones 46a–g with antimicrobial and antimalarial actions.

Figure 40

Structures of acylhydrazone derivatives 47a,b and 48 with antiviral action.

Figure 41

Structures of acylhydrazone derivatives 49–55 with antiviral action.

Figure 42

Structure of acylhydrazone 56 with influenza virus endonuclease inhibitory action.

Figure 43

Structures of acylhydrazones 57–60 with antiparasitic action.

Figure 44

Structures of acylhydrazone derivatives 61–63 with antiparasitic action.

Figure 45

Structure of acylhydrazone 64 with antiparasitic action.

Figure 46

Structure of compound 65 with antiparasitic action on Plasmodium falciparum.

Figure 47

Structures of acylhydrazones 66a,b with antiparasitic action on Trypanosoma cruzi.

Figure 48

Structures of acylhydrazone derivatives 67–72 with anti-inflammatory action.

Figure 49

Structure of the acylhydrazone derivative 73 with anti-inflammatory action.

Figure 50

Structure of the acylhydrazone derivative 74 with non-selective COX inhibitory action.

Figure 51

Structures of compounds 75a–c with anti-inflammatory action.

Figure 52

Structures of acylhydrazones 76a,b and 77 with anti-inflammatory and analgesic actions.

Figure 53

Structure of acylhydrazone 78 with immunosuppressive effect.

Figure 54

Structure of acylhydrazone compound 79 with antiglaucomatous effect.

Figure 55

Structures of compounds 80–82 with activity on the CNS.

Figure 56

Structures of acylhydrazones 83 and 84 with action due to chelation of iron (II) ion.

Figure 57

Structure of acylhydrazone 85 with PDE10A inhibitory action.

Figure 58

Structure of acylhydrazone 86 with inhibitory action of a LOX isoform.

Figure 59

Structures of acylhydrazone derivatives 87a–c and 88a–c with antioxidant action.

Figure 60

Structures of acylhydrazone compounds 89a–e with antidiabetic action.

Figure 61

Structures of acylhydrazone class derivatives 90a–i with antioxidant action.

Figure 62

Structures of acylhydrazones 91a,b with action on the cardiovascular system.

Figure 63

Structures of derivatives 92–95 showing antiplatelet action.

Figure 64

Structures of compounds 96a–e with antithrombotic action.

Figure 65

Structure of acylhydrazone 97 with action on ventricular remodeling.

Figure 66

Structures of acylhydrazone class derivatives 98a–d with vasodilatory action.

Figure 67

Structure of compound 99 with possible use in ischemic stroke.