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Review
. 2020 Dec;35(1):265-279.
doi: 10.1080/14756366.2019.1698036.

Benzothiazole derivatives as anticancer agents

Ali Irfan  1 , Fozia Batool  1 , Syeda Andleeb Zahra Naqvi  1 , Amjad Islam  2 , Sameh M Osman  3 , Alessio Nocentini  4 , Siham A Alissa  5 , Claudiu T Supuran  4
Affiliations
Review

Benzothiazole derivatives as anticancer agents

Ali Irfan et al. J Enzyme Inhib Med Chem. 2020 Dec.

Abstract

Benzothiazole (BTA) belongs to the heterocyclic class of bicyclic compounds. BTA derivatives possesses broad spectrum biological activities such as anticancer, antioxidant, anti-inflammatory, anti-tumour, antiviral, antibacterial, anti-proliferative, anti-diabetic, anti-convulsant, analgesic, anti-tubercular, antimalarial, anti-leishmanial, anti-histaminic and anti-fungal among others. The BTA scaffolds showed a crucial role in the inhibition of the metalloenzyme carbonic anhydrase (CA). In this review an extensive literature survey over the last decade discloses the role of BTA derivatives mainly as anticancer agents. Such compounds are effective against various types of cancer cell lines through a multitude of mechanisms, some of which are poorly studied or understood. The inhibition of tumour associated CAs by BTA derivatives is on the other hand better investigated and such compounds may serve as anticancer leads for the development of agents effective against hypoxic tumours.

Keywords: Benzothiazole; anticancer agent; carbonic anhydrase inhibitor; drug targets; scaffold.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Structure of riluzole, a drug for amyotrophic lateral sclerosis.
Figure 2.
Figure 2.
Substituted phenols containing a flourobenzothiazol scaffold 1 and 2.
Figure 3.
Figure 3.
Substituted thiourea containing benzothiazole derivative 3 and the substituted pyrrolidine based imidazo benzothiazole derivative 4.
Figure 4.
Figure 4.
Substituted fluorophenyl containing benzothiazole urea derivative 5 and 2-substituted cyanophenyl containing benzothiazole urea derivatives 6.
Figure 5.
Figure 5.
Derivative 7–9 discussed in the paper.
Figure 6.
Figure 6.
Benzothiazoles 10 and 11.
Figure 7.
Figure 7.
Indol based hydrazine carboxamide benzothiazole derivative 12.
Figure 8.
Figure 8.
Substituted phenyl imidazole based benzothiazoles 13 and 14.
Figure 9.
Figure 9.
Imidazole based benzothiazole derivative 15.
Figure 10.
Figure 10.
Di-/monochlorobenzenesulfonamide based piperazine benzothiazoles derivative 16 and 17.
Figure 11.
Figure 11.
Pyridine conataining piperazine benzothiazole derivative 18.
Figure 12.
Figure 12.
Oxadiazole based acetamide benzothiazole derivatives 19 and 20.
Figure 13.
Figure 13.
Morpholine based thiourea bromobenzothiazoles 22–24.
Figure 14.
Figure 14.
Morpholine based acetamide benzothiazole 24.
Figure 15.
Figure 15.
Imidazolinyl-substituted thiophene-based benzohiazoles 25 and 26.
Figure 16.
Figure 16.
Substituted thiadiazole based BTAs 27 and 28.
Figure 17.
Figure 17.
Substituted bromopyridine based acetamide benzothiazole derivative 29.
Figure 18.
Figure 18.
Substituted pyridine based acetamide benzothiazole 30 and pyridine containing pyrimidine benzothiazole 31.
Figure 19.
Figure 19.
Pyrazole based benzothiazoles 32 and 33.
Figure 20.
Figure 20.
Structure of pyrimidine based isoxazole derivative 34.
Figure 21.
Figure 21.
Pyrimidine based benzothiazole derivative 35 and 36.
Figure 22.
Figure 22.
Piperidine based acetohydrazide benzothiazole 37.
Figure 23.
Figure 23.
Sulphonamide based methylsulfonyl benzothiazoles 38 and 39.
Figure 24.
Figure 24.
Secondary sulphonamide based acetamide benzothiazole 40.
Figure 25.
Figure 25.
Substituted methoxybenzamide based benzothiazole derivative 41 and chloromethylbenzamide based benzothiazole 42.
Figure 26.
Figure 26.
Benzamide containing benzothiazoles 43 and 44.
Figure 27.
Figure 27.
Substituted difluorobenzamide BTA derivative 45.
Figure 28.
Figure 28.
Hydroxybenzylidine containing quinolone benzothiazole derivative 46 and the nitrobenzylidene quinolone derivative 47.
Figure 29.
Figure 29.
Quinolone based benzothiazole derivative 48.
Figure 30.
Figure 30.
Substituted propanamide/acetamide based benzothiazoles 49 and 50.
Figure 31.
Figure 31.
Dichlorophenyl-chlorobenzothiazole derivative 51.
Figure 32.
Figure 32.
Substituted thioxothiazolidine acetamide benzothiazole derivative 52.
Figure 33.
Figure 33.
Oxothiazolidine based benzothiazole derivative 53 and thiazolidine benzothiazole derivative 54.
Figure 34.
Figure 34.
Chlorobenzyl indole semicarbazide BTA derivative 55 and urea BTA derivative 56.
Figure 35.
Figure 35.
Nitrostyryl containing BTA derivative 57 and fluorostyryl BTA derivative 58.
Figure 36.
Figure 36.
Benzothiophene carboxamide chloroaminobenzothiazole derivative 59.
Figure 37.
Figure 37.
Ru(III) containing methylbenzothiazole derivative 60.
Figure 38.
Figure 38.
Benzimidazole based acetamide methoxybenzothiazole derivative 61 and acetamide ethoxybenzothiazole derivative 62.
Figure 39.
Figure 39.
Hydroxamic acid containing methyl/methoxy benzothiazole scaffolds 63 and 64.
Figure 40.
Figure 40.
Derivative 65–67 discussed in the article.
Figure 41.
Figure 41.
Substituted phenylamino based methoxy benzothiazoles 68 and 69.
Figure 42.
Figure 42.
Substituted phenylthizolidene based benzothiazole derivative 70 and 71.
Figure 43.
Figure 43.
Benzothiazoles with potent CA IX inhibitory action.
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