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Vol 1 | Issue 1 | Apr - Jun 2022                                                                                          Indian J Pharm Drug Stud | 15  

Review Article 

A Comprehensive Review on Synthetic Strategy of Benzothiazole Lead and 

Pharmacological Importance  

Bhoge ND1, Mohite PB2, Deshmukh VK2, Magare BK3  

From, 1Mula Education Society’s Shri Dnyaneshwar Mahavidyalaya, Newasa, Ahmednagar, Maharashtra, 2Mula Education Society’s 

College of Pharmacy, Sonai Tal- Newasa, Dist- Ahmednagar Maharashtra, 3Shivaji Arts, Commerce and Science College, Kannad, 

Aurangabad, Maharashtra, India  

Correspondence to: N.D. Bhoge, Shri Dnyaneshwar Mahavidyalaya Newasa Tal- Newasa, Dist. Ahmednagar, Maharashtra, India. 

Email: nitinbhoge4550@gmail.com  

ABSTRACT 

Background: In recent years heterocyclic compounds analogues and derivatives have attracted wide attention due to their useful 

biological and pharmacological properties. Benzothiazole is among the usually occurring heterocyclic nuclei in many marines as well 

as natural plant products. Benzothiazole is a privileged bicyclic ring system with multiple applications. Objective: To review and 

explore the synthetic strategy of lead and pharmacological importance of Benzthiazole Derivatives. Materials and Methods: A 

literature search was conducted on various database sources (like PubMed, Science Direct) with the help of a combination of different 

keywords: Benzothiazole, thiazole, antitumor, anti-inflammatory activity and anti-convulsant, antioxidant, antimutagenic, anti-diabetic, 

anti-hyperplasia, and antimicrobial. The search was customized by applying the appropriate filter to get the most relevant articles to 

meet the objective of this review. Conclusion: It is known to exhibit a wide range of biological properties including anticancer, 

antimicrobial, and anti-diabetic, anticonvulsant, anti-inflammatory, and anti-viral, anti-tubercular activities. A large number of 

therapeutic agents are synthesized with the help of benzothiazole nucleus. During recent years there have been some interesting 

developments in the biological activities of benzothiazole derivatives. These compounds have special significance in the field of 

medicinal chemistry due to their remarkable pharmacological potentialities. This review is mainly an attempt to present the research 

work reported in the recent scientific literature on different biological activities of benzothiazole compounds.  

Key words: Benzthiazole, Anticancer, anticonvulsant, anti-inflammatory, antimicrobial etc.

antzsch and Waber first described Thiazolein 1887 

and its structure confirmed by Popp in 1889. In 

thiazole, moiety numbering starts from the sulfur 

atom. The basic structure of benzothiazole is the combination 

of a benzene ring fused with 4, 5 positions of thiazole. 

Benzothiazole is one of the most important aromatic 

heterocyclic compounds having a chemical formula 

C7H5NS.It plays a very important role in medicinal chemistry 

as well as in organic chemistry. Today`s most of the drug 

molecule contains a benzothiazole as an important scaffold and 

because of this scaffold, it has therapeutic activity. 

Benzothiazole and its derivatives have tremendous 

applications in synthetic chemistry as well as in 

pharmaceutical chemistry because of its unique structure, 

potent and significant pharmacological activities. 

Benzothiazole  is a combination of two rings six-member 

mono atomic and five-member hetero atomic and both rings 

are responsible for the therapeutic activity.[1] (Fig.1)  

Benzothiazole analogues have also been screened as 

potential therapeutical applications which include anti- viral,  

anti-microbial, anti-diabetic, anti-cancer, antiinflammatory, 

anti-oxidant, anti-fungal, anti-psychotic, anti-leishmanial etc 

[2]. Because of amyloid-binding property derivatives  of 2-

aryl benzothiazoles are screened for radioactive imaging 

moieties in neurodegenerative disorders [3, 4].  

 
Fig.1 Structure of Benzothiazole 

MATERIAL AND METHODS 

A literature search was conducted on various database sources 

(like PubMed, Science Direct) with the help of a combination 

H 



Bhoge et al.                                                                                       Pharmacological Importance of Benzothiazole Lead  

Vol 1 | Issue 1 | Apr - Jun 2022                                                                                          Indian J Pharm Drug Stud | 16  

of different keywords: Benzothiazole, thiazole, antitumor, 

anti-inflammatory activity, and anticonvulsant, anti-oxidant, 

anti-mutagenic, anti-diabetic, anti-hyperplasia, and anti-

microbial. The search was customized by applying the 

appropriate filter to get the most relevant articles to meet the 

objective of this review 

Synthetic and Biological Active Strategy of Benzothiazole 

Derivatives  

Many researchers are using various methodologies. 

Benzothiazole derivative can be synthesized by using 

conventional, microwave method or by other green chemistry 

method. In this review article we are focusing on recent 

methods which are available for the synthesis of benzothiazole 

derivatives and their biological activities. 

Hebishy synthesized a bis- and poly (benzimidazoles) and 

Benzothiazoles derivatives by using corresponding bis- and 

poly (aldehyde) with ophenylenediamine or 2-

aminothiophenol, respectively, in ethanol at boiling 

temperature in presence of sodium hydrogen sulphate, further 

these synthesized derivatives were screened for anticancer 

activities against human breast adeno carcinoma cell line 

(MCF-7), liver cancer cell line (HepG-2), and epithelial 

colorectal adeno carcinoma cells (CaCO-2). But among all 

derivatives Hexakis (benzothiazole) showed a highest activity 

against HepG-2 cell lines with IC50 values of 21.16 and MCF-

7 cell lines with IC50 values of 13.25 μM [5].  

Racanéa et al., reported about a synthetic method for the 

synthesis of benzothiazole based derivative and most of the 

derivatives showed cytotoxic activity which performed using 

the MTT assay method. Compounds 2a, 2b, 2c, and 2d (Fig. 

2) were then selected for examining their in vitro enzyme 

inhibitory activities against EGFR, HER2 and TS enzymes 

using lapatinib and 5FU as standards. Furthermore, cell cycle 

analysis and apoptosis induction detection were also evaluated 

[6].  

 
Fig.2 Compounds chosen for MTT assay  

Asatkar et al., reported that the aqueous extracts of rice husk 

derived chemically activated carbon acts as a catalyzed for the 

synthesis of benzothiazole, benzoxazole and N-benzimidazole 

in  room temperature by converting 2-aminothiophenol, 

2amino phenol and ortho-phenylene di-amine with aromatic 

aldehydes with 98%yeild [7] (Fig. 3) 

 
Fig. 3 Synthesis of benzothiazole, benzoxazole and N-

benzimidazole from rice husk  

A series of novel pyrido [2, 1-b] benzothiazole and pyrido 

 [2, 1-b] benzoimidazole  derivatives were synthesized by 

reacting with N-aryl-2-cyano-3,3-bis (methylthio) acrylamide 

with benzothiazole acetonitrile and benzoimidazole acetonitrile, 

respectively, while Nsubstituted 2-pyridyl-benzothiazole 

derivatives were synthesized by reacting 2- benzo [d] thiazol-2-

yl) -3-(dimethylamino) acrylo nitrile with either 

cyanoacetamide, aryl cyanoacetamides or 2-cyano-N'- (4-

substitutedbenzylidene) acetohydrazide (Azzam et al).  

Furthermore, synthesized compound tested for 

fluorescence measurements, the compound N-substituted 2- 

pyridylbenzothiazole derivatives shows fluorescence 

properties with high quantum yields upto 0.29. The 

antimicrobial study of synthesized compound revealed that 

triazolo-pyridone had the highest potency among all tested 

compounds against Escherichia coli, Klebsiella pneumonia and 

Staphylococcus aureus while pyrido [2, 1-b] benzoimidazole 

derivatives 4a and 4b had the highest potency over other 

compounds against Candida albicans [8] (Fig.4).  

 
Fig.4 (3) triazolo-pyridone, (4) Benzoimidazole derivatives 

4a and 4b with more efficacy against Candida albicans   

Ermis et al described the synthesis of a series of thiophene-

benzothiazole derivative amine compounds in good yields by 



Bhoge et al.                                                                                       Pharmacological Importance of Benzothiazole Lead  

Vol 1 | Issue 1 | Apr - Jun 2022                                                                                          Indian J Pharm Drug Stud | 17  

reduction of corresponding imine derivative which is obtain 

from aromatic aldehyde and 2aminobenzothiazole by 

microwave reaction. The characterizations of all compounds 

were performed by FTIR, 1H and 13C NMR and single crystal 

X-ray diffraction method [9] (Fig.5). Azzam et al. prepared a 

series of N-sulfonamide-2-pyridone derivatives which 

contains benzothiazole moiety via the reaction of 

benzothiazole sulfonyl hydrazide with sodium salts of both 

(hydroxymethylene) cycloalkanones and unsaturated ketones, 

as well as)  

 
Hethoxymethylene derivatives. The prepared compounds were 

screened for in vitro for their antiviral activities against the 

HSV-1, HAVHM175, HCVcc genotype 4, CBV4, and HAdV7 

viruses. Among prepared compound, five compounds were 

found to possess viral reduction of 50% or more against CBV4 

with significant IC50, CC50, and SI values. In the case of 

HSV-1 and HAV HM175 viruses, three compounds have 

shown more than 50% reduction, while in the case of HCVcc 

genotype 4 and HAdV7 viruses, only two compounds 

demonstrated more than 50% reduction. The two most potent 

compounds against HSV-1 virus, 6a and 6b, were evaluated for 

their inhibitory activity against USP7 [10] (Fig. 6).  

 

A series of 2-pyrimidylbenzothiazoles derivatives 

containing amino or sulfonamide moieties at the C2 position 

of the pyrimidine ring were synthesized by Azzam et al. by 

subsequent reaction of guanidine or Naryl sulfonated 

guanidine with different derivatives of ylidene benzothiazole. 

The newly synthesized compounds were evaluated for their 

antiviral activity against HSV-1, COB4, HAV HM 175, ED-

43/SG-Feo (VYG) replicon of HCV genotype 4a, and HAdV7. 

Nine derivatives were shows high cytotoxicity concentration 

and more than 50% viral reduction. Another five compounds 

against HSV-1 have been also evaluated against Hsp90α with 

their activities compared to that of the reference drug 

acyclovir. The five potent compounds 7a, 7b, 14b, 14g, and 

14h against HSV-1 have also presented inhibitory activity 

against the Hsp90α protein with IC50 in the range of 

4.87−10.47 μg/mL[11] (Fig.7).  

 
Fig. 7 Synthesis of 2-mercapto -benzazole derivatives  

 

A green protocol given by Vessally et al. for the synthesis 

of 2-mercapto-benzazole derivatives 9a by using low-cost and 

nontoxic potassium thiocyanate in water. The reactions 

proceeded smoothly under catalyst- and ligandfree conditions 

to give the corresponding products in good to excellent yields 

[12] (Fig.7).  

 

Abdelgawad et al. reported a synthesis of new series of 

benzothiazole/benzoxazole and/or benzoimidazole substituted 

pyrazole derivatives 10, 11 and 12 and it were evaluated for 

anti-proliferative agents. This work revealed that substituting 

pyrazole ring with an acetyl or phenyl moiety at N-2 of the 

pyrazo linone nucleus as shown in the target candidates 11 and 

12 increased the anti-proliferative activity of these compounds 

comparing with unsubstituted derivatives 10. Moreover, 2-

acetyl-4[(3-(1H-benzimidazol-yl) phenyl] hydrazono-5-

methyl2,4-dihydropyrazol-3-one (11) was the most active 

compound against both MCF-7 and A549 cell lines with half 

maximal inhibitory concentrations (IC50) = 6.42 and 8.46 lM, 

respectively [13]  

Almehmadi et al. synthesized a novel macromolecule 

encompassing benzothiazole- 1, 2, 3-triazole containing 

hydrazone. The synthesized compounds were evaluated for 

anticancer activities with A549 and H1299 lung cancer cell 



Bhoge et al.                                                                                       Pharmacological Importance of Benzothiazole Lead  

Vol 1 | Issue 1 | Apr - Jun 2022                                                                                          Indian J Pharm Drug Stud | 18  

lines. The anticancer activities ranged from 55 to 90%. DNA 

binding study was also carried out to see the mechanism of 

action and the DNA binding constants were of good value 

ranging from of 2.0 ×10 5 and 14.7 ×10 5 M −1; indicating 

good interactions of the reported molecules with DNA. It 

was observed that compound 13, 14, 15 and 16, 17 &18 were 

quite good active as anticancer drugs [14] (Fig.9)  

Asgarshamsi et al. were performed a reaction between 

para hydroxyl benzaldehyde and amino benzothiazole 

derivatives. The synthesized derivative was further 

evaluated for scavenging activity. Various electronic and 

energetic descriptors such as high occupied molecular 

orbital and low unoccupied molecular orbital energy gaps, 

bonding dissociation enthalpy of OH bond, ionization 

potential, electron affinity, hardness, softness, and spin 

density of the radical and neutral species were calculated. 

FT calculations with B3LYP hybrid functional and 6-311++ 

G** basis set in the polarizable continuum model were 

utilized to obtain these descriptors. Ascorbic acid showed 

the best DPPH scavenging activity. But 19th band showed a 

promising anti-oxidant activity. The values of EHOMO for 

19a and 19b were closer to zero, thus, they showed the best 

scavenging activities. Dadmal et al. reported the synthesis of 

a series of new triazole and isoxazole linked benzothiazole 

derivatives were synthesized. Anticancer evaluation against 

two different cell lines revealed that all these derivatives 

showed significant anticancer activity against HeLa and 

A549 cell lines.  

 
Fig. 8 Novel macromolecules encompassing benzothiazole  

 
Fig. 9 Para hydroxyl benzaldehyde and amino 

benzothiazole derivative showing antoxidant activity  

Reviewing these recent advances in benzothiazole 

derivative we will go for synthesis of some novel 

benzothiazole derivatives and synthesized compound will be 

evaluated for possible biological activities such as anti-fungal, 

anti-bacterial, anti-viral, anti-microbial, anti-diabetic, 

anticancer, anti-inflammatory, antioxidant etc.   

 
Fig. 10 New triazole and isoxazole linked benzothiazole 

derivatives  

Highly effective compounds (20a-b and 21a-c) have shown less 

than 4.5 μM concentration in their IC50 values on human 

cervical (HeLa) and lung (A549) cancer cell line and these 

compounds inducing apoptosis to cancerous cells through 

caspase dependent apoptotic process via the mitochondrial 

pathway. From these study compounds 21a-chas identified as 

most promising compounds which show higher cytotoxicity in 

human cervical and lung cancer cell line than the other 

compounds and can be taken up for further in vivo cancer 

studies that may be of interest in cancer chemoprevention [16] 

(Fig.10).  

CONCLUSION  

The present review highlights the use of benzothiazole moiety as 

a template for development of newer therapeutic agents. 

Biological properties of the nucleus include anti-cancer, anti-

diabetic, analgesic, anti-inflammatory and antimicrobial. With 

proper designing and structure activity relationship studies of 

known benzothiazole, prospective compounds can be designed 

and synthesized for a variety of biological activities. 

Benzothiazole scaffold is a versatile and multifunctional molecule 

which possess therapeutic effect in various disease like cancer, 

diabetes.  

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Bhoge et al.                                                                                       Pharmacological Importance of Benzothiazole Lead  

Vol 1 | Issue 1 | Apr - Jun 2022                                                                                          Indian J Pharm Drug Stud | 19  

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How to cite this article: Bhoge ND, Mohite PB, 

Deshmukh VK, et al. A Comprehensive Review on 

Synthetic Strategy of Benzothiazole Lead and 

Pharmacological Importance. Indian J Pharm Drug Stud. 

2022; 1(1): 15-19.  

Funding: None;               Conflict of Interest: None Stated 

 


