Indole - a promising pharmacophore in recent antiviral drug discovery

Abstract

The bicyclic molecule indole has been in the limelight because of its numerous pharmacological potencies. It is used as an excellent scaffold in drug discovery of medicinal drugs such as antimicrobials, anticancer agents, antihypertensives, anti-proliferative agents and anti-inflammatory agents. In spite of its diverse therapeutic activity, it is used as a key pharmacophore in synthesizing the most potent biological agents. Besides, viral infections are ubiquitous and their prevention and cure have become a great challenge. In this regard, the design of indole-containing antiviral drugs is accomplished to combat viral infections. A lot of research is being carried out towards antiviral drug discovery by many researchers round the clock. Herein, the antiviral activity of recently discovered indole scaffolds is compiled and critically evaluated to give a meaningful summary. In addition, the structure-activity relationship of remarkable antiviral agents is discussed. Also, the structural motifs attributed to noteworthy antiviral properties are highlighted to guide future antiviral research.

Fig. 1. Illustration of the structure of indole.

Fig. 2. Depiction of N-benzylated tetrahydroindoles [reproduced from ref. 25 with permission from Elsevier, copyright 2020].

Fig. 3. Structures of aminal analogs of MK-8742 [reproduced from ref. 26 with permission from Elsevier, copyright 2020].

Fig. 4. Structures of halogenated MK-8742 derivatives [reproduced from ref. 27 with permission from Elsevier, copyright 2020].

Fig. 5. Structures of noteworthy indole-containing HCV inhibitors [reproduced from ref. 28 with permission from Elsevier, copyright 2020].

Fig. 6. Structures of t-butylaniline acrylamide analogs of indole.

Fig. 7. Illustration of structures of N-substituted acrylamide indole derivatives [reproduced from ref. 31 with permission from Wiley, copyright 2020].

Fig. 8. Chemical structures of indole-pyrazolone derivatives [reproduced from ref. 32 with permission from Elsevier, copyright 2020].

Fig. 9. Illustration of potent inhibitors of HCV 1b genotype.

Fig. 10. Structures of MK-8742 derivatives with mixed caps [reproduced from ref. 34 with permission from Elsevier, copyright 2020].

Fig. 11. Depiction of structures of tricyclic fluoroindole derivatives [reproduced from ref. 35 with permission from Elsevier, copyright 2020].

Fig. 12. Illustration of structural analogs of umifenovir [reproduced from ref. 41 with permission from Elsevier, copyright 2020].

Fig. 13. Structures of remarkable NL4.3X4 and Bal R5 inhibitory agents.

Fig. 14. Structure of the indole glyoxamide derivatives [reproduced from ref. 43 with permission from Elsevier, copyright 2020].

Fig. 15. Depiction of structures of dihydroxyindole carboxylic acid derivatives [reproduced from ref. 44 with permission from Elsevier, copyright 2020].

Fig. 16. Structure of a remarkable anti-HIV-1 inhibitor.

Fig. 17. Structures of halo-indole derivatives with HIV integrase inhibitory activity [reproduced from ref. 48 with permission from Wiley, copyright 2020].

Fig. 18. Structures of the most potent anti-HIV agents [reproduced from ref. 50 with permission from Elsevier, copyright 2020].

Fig. 19. Structures of indolylarylsulfones with an aromatic/heterocyclic tail [reproduced from ref. 51 with permission from American Chemical Society, copyright 2020].

Fig. 20. Depiction of structures of 5-fluoroindole derivatives as anti-HIV agents [reproduced from ref. 52 with permission from Wiley, copyright 2020].

Fig. 21. Structure of nucleoside analog with moderate anti-DENV activity.

Fig. 22. Structures of spiro-indolinone scaffolds [reproduced from ref. 60 with permission from American Chemical Society, copyright 2020].

Fig. 23. Illustration of structures of indoles connecting diaryl rings [reproduced from ref. 61 with permission from the American Chemical Society, copyright 2020].

Fig. 24. Structures of 5-chloroindole derivatives with decent anti-DENV-2 activity.

Fig. 25. Chemical structures of dihydroindole-containing natural products.

Fig. 26. Depiction of structures of harmol and 9-methylharmine [reproduced from ref. 67 with permission from Elsevier, copyright 2020].

Fig. 27. Illustration of the active molecule of Peganum harmala83 and dihydropyridoindole derivative (harmaline) 84 [reproduced from ref. 76 and with permission from Elsevier, copyright 2020].

Fig. 28. Chemical structure of arbidol [reproduced from ref. 78 with permission from Elsevier, copyright 2020].

Fig. 29. Depiction of structures of arbidol derivatives [reproduced from ref. 79 with permission from Microbial Society, copyright 2020].

Fig. 30. Structures of thiazolidinone-appending pyridoindole derivatives [reproduced from ref. 81 with permission from Elsevier, copyright 2020].

Fig. 31. Structures of substituted pyridoindole analogs [reproduced from ref. 82 with permission from Elsevier, copyright 2020].

Fig. 32. Depiction of chemical structures of 3,3-dimethylindole derivatives.

Fig. 33. Structures of indole-3-carboxylic acid analogs [reproduced from ref. 90 with permission from springer, copyright 2020].

Fig. 34. Illustration of structures of indole–flutimide derivatives.

Fig. 35. Chemical structures of carboxamide-tethered indole-spirothiazolidinones [reproduced from ref. 92 with permission from Elsevier, copyright 2020].

Fig. 36. Illustration of the structure of a bisindole derivative [reproduced from ref. 95 with permission from Tailor & Francis, copyright 2020].

Atukuri Dorababu