An insight on medicinal attributes of 1,2,4-triazoles

Abstract

The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

Keywords: 1,2,4-Triazole; Enzyme inhibitors; Hybrid compounds; Molecular interactions; Pharmacological activities; Structure-activity relationship.

Graphical abstract

Fig. 1

Tautomeric forms of 1,2,4-triazole.

Fig. 2

Clinically used drugs having 1,2,4-triazole scaffold.

Fig. 3

SAR and antifungal activity profiles of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-4-substituted derivatives.

Fig. 3

SAR and antifungal activity profiles of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-4-substituted derivatives.

Fig. 4

SAR and antifungal activity profiles of 1-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-4-substituted derivatives 16–20.

Fig. 5

1,2,4-Triazole derivatives with antifungal activity.

Fig. 6

1,2,4-Triazole-quinolone hybrids with antibacterial activity.

Fig. 7

SAR and antibacterial activity studies of fused 1,2,4-triazole derivatives.

Fig. 8

Mercapto/thione/thio-substituted 1,2,4-triazole derivatives with antibacterial activity.

Fig. 9

1,2,4-Triazoles derivatives 52–56 with antibacterial activity.

Fig. 10

1,2,4-Triazole derivatives as PIM inhibitors.

Fig. 11

(a) 1,2,4-Triazole derivatives as EGFR inhibitors. (b) 3D interactions of compound 58a with amino acid residues in the catalytic channel of MetAP2 enzyme.

Fig. 12

(A) 1,2,4-Triazole derivatives as VEGFR inhibitors. (B) Predicted binding mode of compound 59a in the active site of VEGFR-2 which shows H-bond between CO group and Lys868.

Fig. 13

1,2,4-Triazole derivatives as tyrosine kinases inhibitors.

Fig. 14

1,2,4-Triazole derivatives as c-MET kinase inhibitors.

Fig. 15

1,2,4-Triazole derivatives as thymidine phosphorylase inhibitors.

Fig. 16

1,2,4-Triazole derivatives as topoisomerase inhibitors.

Fig. 17

1,2,4-Triazole derivatives as methionine aminopeptidase type II inhibitors.

Fig. 18

1,2,4-Triazole derivatives as COX-2 inhibitors.

Fig. 19

1,2,4-Triazole derivatives as carbonic anhydrase inhibitors.

Fig. 20

1,2,4-Triazole derivatives as aromatase inhibitors.

Fig. 21

1,2,4-Triazole derivatives as LSD1/KDM1A inhibitors and binding of compound 89a and FAD (colored in green and yellow, respectively) in the active site of LSD1. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 22

1,2,4-Triazole derivatives as TNKS inhibitors.

Fig. 23

1,2,4-Triazole derivatives as BRD4 inhibitors.

Fig. 24

1,2,4-Triazole derivatives 92–99 as tubulin polymerization inhibitors.

Fig. 25

1,2,4-Triazole derivatives 100–104 as tubulin polymerization inhibitors.

Fig. 26

Fused 1,2,4-triazole derivatives 105–113 as anticancer agents.

Fig. 27

Fused 1,2,4-triazole derivatives 114–122 as anticancer agents.

Fig. 28

Fused 1,2,4-triazole derivatives 123–126 as anticancer agents.

Fig. 29

Fused 1,2,4-triazole derivatives 127–132 as anticancer agents.

Fig. 30

Thio-substituted 1,2,4-triazole derivatives as anticancer agents.

Fig. 31

Thio-substituted 1,2,4-triazole derivatives as anticancer agents. Compound 140 interaction with key residues in the active site of EGFR enzyme.

Fig. 32

(a) Coumarin-1,2,4-triazole derivatives as anticancer agents. (b) Stereoview of compound 145i docked into the active site of EGFR-TKD which shows two hydrogen binding interaction of oxygen atom of carbonyl group at coumarin ring with hydrogen atom of the amino acid residue Lys721.

Fig. 33

4-(1H-1,2,4-Triazol-1-yl)benzoic acid hybrids as anticancer agents.

Fig. 34

Fused 1,2,4-triazole derivatives as anticonvulsant agents.

Fig. 35

Substituted triazolthiones with anticonvulsant activity.

Fig. 36

1,2,4-Triazoles derivatives 164–168 with anticonvulsant activity.

Fig. 37

Substituted triazolthiones 169–177 with anti-TB potential.

Fig. 38

Fused 1,2,4-triazoles anti-TB potential.

Fig. 39

Various 1,2,4-triazoles with anti-TB potential.

Fig. 40

1,2,4-Triazole derivatives as antiviral agents.

Fig. 41

1,2,4-Triazole derivatives as anti-HIV agents.

Fig. 42

1,2,4-Triazole derivates as antimalarial agents.

Fig. 43

1,2,4-Triazole derivates as antitrypanosomal agents.

Fig. 44

Kinetoplastid proteasome inhibitors.

Fig. 45

1,2,4-Triazole derivates as antileishmanial agents.

Fig. 46

1,2,4-Triazole derivates as anti-inflammatory agents and illustration of the binding of compound 241a in the COX-2 active site.

Fig. 47

Fused 1,2,4-triazole derivates as anti-inflammatory agents.

Fig. 48

1,2,4-Triazolo derivatives with miscellaneous activity.