Introduction

The phenomenon of resistance to antibiotics is developing all over the globe, threatening the future of health care services in developed countries in the future, and on the other hand, in developing countries the lack of adequate surveillance, threatening emergence of outbreaks of multidrug-resistant pathogens (Prestinaci, Pezzotti, & Pantosti, 2015). Unfortunately, the appearance of a novel coronavirus (SARS-CoV-2) in China in late 2019, which was developed rapidly to become an international pandemic, under the absence of any treatment, requires an urgent search for a cure (Kothai & Arul, 2019).

Interestingly, the development in the biological evaluation of heterocyclic molecules has undergone numerous changes. The advancement in molecular biology has eased the design of new molecules based on their mechanism of action, benzothiazole and its derivatives belong to an enormously important family of synthetic compounds of heterocyclic systems containing a benzene ring fused with a thiazole ring, they contain extended π-delocalized systems which are capable of binding to DNA molecules via π–π interactions, therefore, exhibit multiple biological properties, for instance, antitumor, antiinfective, antifungal or antihelmintic activities (Pavlović, Soldin, Popović, & &tralić-Kulenović, 2007). They are among the most important classes of molecules having a common heterocyclic scaffold in several biologically active and medicinally significant compounds hence, are used worldwide for a variety of therapeutic applications.Recently, benzothiazole derivatives have been evaluated as potential amyloid-binding diagnostic agents in neurodegenerative disease. (Henriksen et al., 2007; Mathis et al., 2003) and as selective fatty acid amide hydrolase inhibitors (Wang et al., 2009). Benzothiazoles with a bicyclic ring system. 2-amino benzotriazoles were intensively studied in the 1950s as central muscles relaxants when the pharmacological profile of Riluzole (Bryson, Fulton, & Benfield, 1996) was discovered. After that, the benzothiazoles scaffold have great attention due to their potent and significant biological activities. It has excellent pharmaceutical importance; hence, the synthesis of these compoundsis of considerable interest. The current mini-review demonstrates the antimicrobial and antiviral potential of benzothiazole derivatives, which could be used in pharmaceutical formulations after evaluating its safety as a drug.

Synthesis of bioactive benzothiazole derivatives

A series of Schiff bases of benzothiazole derivatives were synthesized (Soni, Ranawat, Sharma, Bhandari, & Sharma, 2010) .By condensation of 5-[2-(1,3-benzothiazol-2-yl-amino) ethyl]-4-amino-3-mercapto-(4H)-1,2,4-triazole (1) with appropriate aromatic aldehydes afforded 5-[2-(1,3- benzothiazol-2-yl-amino)ethyl]-4-(arylideneamino)-3-mercapto-(4H)-1,2,4-triazoles (2a-g). Figure 1.

A simple and efficient synthetic method for novel derivatives of curcumin. 4H-Pyrimido[2,1-b]benzothiazole (3a-h) have been developed (Sahu, Sahu, Gupta, Thavaselvam, & Agarwal, 2012). These compounds were synthesized by the three-component reaction of curcumin, substituted aromatic aldehydes and 2-amino benzothiazole using pyridine under solvent and solvent-free conditions Figure 2.

The benzothiazole-2-yl-di-prop-2-ynyl-amine(4)was synthesizedin good yield by simple alkylation involving reaction of2-aminobenzothiazole and propargyl bromide (Singh, Tilak, Nath, Awasthi, & Agarwal, 2013). The resulting compound was further reacted with various substituted aromatic azides (a-t) to give 20 different compounds (5a-t). Figure 3.

(Seenaiah et al., 2014) were found that the synthesizedcompound 4-(benzothiazole-2-yl)methylthio)-6-methyl pyrimidine-2-ylthio)methyl)benzothiazole(6)displayed higher activity this may be due to more flexibility of these compounds (Seenaiah et al., 2014). Figure 4.

Synthesis of 4-(1,3-benzothiazole-2-ylsulfanyl)-5,7-dinitro-4,7-dihydro-2,1,3-benzoxadiazole hydrate (9)(Chugunova et al., 2015) by mixing equimolar amounts of benzofuroxan and 2- mercaptobenzothiazole in acetonitrile and presence of basic alumina, the benzothiazolederivative seven was isolated.Figure 5.

Twoseries of compounds contain pyrazole moiety (8a,b) was synthesized. (Gabr et al., 2015), these prepared by refluxing the hydrazine derivative with ethyl 3-oxo-2-((2-substituted phenyl)hydrazo-no) but anoates, (Pareek, Joseph, & Seth, 2009) (Pareek et al., 2009), andisatin and arylidene (9a-c) moiety into the benzothiazole ring to verify the importance of 2-hydrazinobenzothiazole derivatives, (Barot, Mallika, Sutariya, Shukla, & &nargund, 2010) for the antimicrobial activity. Figure 6.

(Asati, Sahu, Rathore, Sahu, & Kohli, 2015) reports the synthesis of some new 1,3-benzothiazole-2-yl-hydrazonederivatives (10a, b) and they're in vitro antibacterial and antifungal screening. Figure 7.

Benzothiazole moiety substituted with Guanidine moiety (15, 16, 17) were synthesized (Venkatesh & Tiwari, 2016) which showed differential activity against the tested fungus and bacteria. Figure 8.

(Thakkar, Thakor, Ray, Doshi, & Thakkar, 2017) synthesized and characterized Schiff bases with benzothiazole moiety(18a –g,19, 20,21), due to their potential activity against malarial and microbial infections. Figure 9.

Methylsulfonylbenzothiazoles (MSBT) derivatives)22, 23, 24, 25, 26)were synthesized (Lad et al., 2017), from sequential reactions on 5- ethoxy-2- (methylsulfonyl) benzo[d]thiazole such as nitration, reduction, sulfonation, dealkylation, etc. To investigate their antimicrobial and anticancer activities. Figure 10.

(Ammar, Alturiqi, Alaghaz, & Zayed, 2018) synthesized 2-(2-mercaptophenyl) benzothiazole complexes (27,28,29,30)via condensation of 2-mercaptoaniline and 2-mercaptobenzoic acid and study their in-vitro antimicrobial activity. Figure 11.

(Mishra et al., 2019) reported the designing, synthesis and antimicrobial activity of azo linked substitutedbenzothiazole derivative (31) Figure 12.

(Ghanavatkar, Mishra, Mali, Chaudhari, & Sekar, 2019) Synthesize azo clubbed benzothiazole derivatives (32,33) by diazotization reaction, and in-vitro antimicrobial screening studies were performed Figure 13.

(Ismail, Abdulwahab, Nossier, Menofy, & Abdelkhalek, 2020) screened novel synthesized benzothiazole-based compounds for antimicrobial activity, the derivatives N1-(4-fluorophenyl)-N3-(6-sulfamoylbenzo[d]thiazol-2-yl)malonamide (34) and Ethyl 2-(3-methyl-4-oxothiazolidin-2-ylidene)-3-oxo-3-(6-sulfamoylbenzo[d]thiazol-2-yl)amino)propanoate (35)were more potent than reference standard ciprofloxacin against methicillin-resistant Staphylococcus aureus (MRSA)and a multi-drug resistant clinical isolate of Enterococcus faecium. Figure 14.

Antimicrobial potential of benzothiazole

Numerous studies showed that some synthesized benzothiazole compounds showed noticeable antibacterial and antifungal activity. It was reported that New compounds containing both benzofuroxan and benzothiazole scaffolds revealed bacteriostatic properties towards Vibrio spp. in the concentration up to 10⁷ M and also were able to activate the 1st type Quorum Sensing system effectively (Chugunova et al., 2015). In an interesting study, Singh et al. (2013) have designed and synthesized some benzothiazoleAnalogs, these novel compounds showed remarkable antibacterial and antifungal activity against most tested microorganisms, with low MIC and two-fold more active than the standard antibiotic (Ciprofloxacin). (Sahu et al., 2012) have synthesized and evaluated the antimicrobial activity of a new, one-pot, efficient and straightforward procedure for 4H-pyrimido[2,1-b]benzothiazole (4a-h), pyrazole (6a-d) and benzylidene (7a-d) derivatives of curcumin under solvent and solvent-free conditions in the microwave. These novel compounds recorded noticeable antimicrobial effect against both of the Gram-positive bacterial (Staphylococcus aureus, Bacillus cereus), Gram-negative bacteria (Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, and Providencia rettgeri) and fungi (Aspergillus niger, Aspergillus fumigates, Aspergillus flavus). (Soni et al., 2010) cited that the novel series of Schiff bases of benzothiazole derivatives that have been synthesized by his team exhibited varying degrees of antimicrobial activity against Bacillus subtilis, Escherichia coli, Streptomyces griseus, Candida albicans and Aspergillus niger; Moreover, those researchers observed that the antimicrobial activity increases with p-substitution and decreases when there is an o-substitution.

Antiviral potential of benzothiazole moieties

Since decades, many scientific studies were conducted to innovate antiviral drugs. Some interesting studies on benzothiazole derivatives recorded promising antiviral activities, such as 3-(2-ethylthio-6-benzothiazolylaminomethyl)-2-benzothiazolinethione which showed high antiviral activity (in vitro) against Newcastle disease virus, vaccinia virus and western equine encephalomyelitis virus (Rada, Holbova, Mikulasek, Sidoova, & &gvozdjakova, 1979).1, 2, 4-thiadiazol-2 ylcyanamide; is an example of benzothiazole derivatives of significant antiviral activity against Human parainfluenza viruses (Falsey, 2012). To the best of our knowledge, no studies were conducted on the antiviral activity of Benzothiazole moieties and their derivatives; Accordingly, we recommend the scientific community for further investigation on this class of interesting compounds, which could lead to an effective anti-SARS-CoV-2 drug. Finally, the safety of these synthesized compounds should be evaluated, a study conducted in Turkey reported that 5-chloro-1'-methyl-5'-nitro-3H-spiro[1,3-benzothiazole-2,3'-indole]-2'(1'H)-one which showed some degree of antiviral features was cytotoxic (Akdemir, Karali, Ermut, & Tan, 2013).The following are some structures of benzothiazole moieties: 3-(2-ethylthio-6-benzothiazolylaminomethyl)-2-benzothiazolinethione (36) was examined (Rada et al., 1979) which show antiviral activity. Figure 15.

(Falsey, 2012) referred to the antiviral activity of 1, 2, 4-thiadiazol-2 ylcyanamide (37). Figure 16.

5-Chloro-1'-methyl-5'-nitro-3H-spiro[1,3-benzothiazole-2,3'-indole]-2'(1'H)-one (38) was synthesized and evaluated for antimicrobial and antiviral activities (Akdemir et al., 2013). Figure 17.

Conclusion

In nature, benzothiazole derivatives enter in some biological compounds such as the structure of vitamin B12. In the laboratory, numerous benzothiazole compounds showed noticeable antimicrobial and antiviral activity; some of them are mentioned in the current mini-review. These interesting synthesized heterocyclic compounds are recommended to be tested against various pathogens as well as the emerging virus SARS-CoV-2, causing Covid-19 disease.

Acknowledgements

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Conflict of Interest

The author declares that there is no conflict of interest