A COMPREHENSIVE REVIEW ON THE BIOLOGICAL ASPECTS OF EMERGING BENZOTHIAZOLE

About Author
Ekta Khare*, Saswati Sharma, Yuvraj Singh, Priyanka Keshri
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, I.T.M. University, Gwalior,
Madhya Pradesh-474001, India
ektakhare23@gmail.com

ABSTRACT :
As of late heterocyclic mixes analogs and subordinates have pulled in wide consideration because of their helpful natural and pharmacological properties. Benzothiazole is among the typically happening heterocyclic cores in numerous marine just as characteristic plant items. Benzothiazole is a special bicyclic ring framework with various applications. It is known to show a wide scope of organic properties including anticancer, antimicrobial, and antidiabetic, anticonvulsant, calming, antiviral, antitubercular exercises. An enormous number of restorative specialists are combined with the assistance of benzothiazole core. During late years there have been some intriguing advancements with regards to the natural exercises of benzothiazole subsidiaries. These mixes have unique centrality in the field of therapeutic science because of their exceptional pharmacological possibilities. This audit is mostly an endeavor to introduce the examination work revealed in the ongoing logical writing on various organic exercises of benzothiazole mixes.

INTRODUCTION:
Benzothiazole is an organic heterocyclic ring system that is a chemical result of the fusion between benzene and thiazole. Its molecular weight is 135.19 g/mol. Its derivatives were found to be possessing and exhibiting a wide range of astounding medicinal properties some of them being anticancer, antimicrobial, antidiabetic, anticonvulsant, anti-inflammatory, antiviral, antitubercular, antihelminthic, and anti-fungal, anti-malarial. As BT demonstrates such a wide spectrum of activity it for sure is very important for drug development. Its derivatives are believed to be useful for the treatment of diseases like brain ischemia, several neurogenerative disorders, Huntington's disease, and Cancer.

METHOD:
A literature search was conducted on various database sources (like PubMed, ScienceDirect) with the help of a combination of different keywords such as Benzothiazole, thiazole, antitumor, anti-inflammatory activity, anticonvulsant, antioxidant, anti-mutagenic, 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.
Clinical Activity:
Anticancer activities:
After cardiovascular diseases, Cancer is the 2nd largest disease worldwide which causes the majority of deaths. The BT nucleus with various substitutions shows antitumor activity. Substituted 2-(4-aminophenyl)benzothiazole is one such compound that represents a potent, highly selective, and new class of antitumor agents. After a thorough examination, it shows antitumor activity in human cell lines of breast, colon, lung, ovarian, and renal carcinoma.

According to the literature study of Benzothiazole derivatives as anticancer agents are
• Fluorinated derivatives
• Imidazole based benzothiazole derivatives
• Piperazine based benzothiazole derivatives
• Oxadiazole based benzothiazole derivatives
• Morpholine- thiourea based benzothiazole derivatives
• Thiophene based benzothiazole derivatives
• Thiadiazole based benzothiazole derivatives
• Substituted pyridine based benzothiazole derivatives
• Pyrazole based benzothiazole derivatives
• Pyrimidine based benzothiazole derivatives
• Piperidine based benzothiazole derivatives
• Secondary sulphonamide benzothiazole derivatives
• Benzamide based benzothiazole derivatives
• Quinolone based benzothiazole derivatives

Benzothiazole derivatives that show carbonic anhydrase inhibitory and antitumor action are sulphonamides, their isosteres, and their inorganic ions.

Antimicrobial activity:
U.K. Singh et.al reported the synthesis of Schiff's and N-Mannich bases of isatin and its derivatives with 4-amino-N-carbamimidoyl benzene sulfonamide3 was tested for antibacterial activity by MIC method on strains S.aureus, B.pumulis, B.subtilis, E.coli, S.abony, K pneumonia.These compounds exhibited very significant and better antibacterial activity.

4-amino-N-carbamimidoyl benzene sulfonamide

Ramachandran et al. reported the synthesis of Schiff and mannich bases of Isatin derivatives. These were also tested for anti-microbial activity but by cup and plate method on strains of staphylococcus aureus, streptococcus pyogenes, Escherichia coli, klebsilla aerogenes, and candida albicans. Most of them displayed greater antibacterial and antifungal activities when compared to standard drugs.

Antitubercular activity:
Tuberculosis is a serious bacterial infection that affects the lungs and spreads easily meaning it is highly contagious. Even though it is partly preventable, the keyword here is partly. Scientists all over the world are researching this topic.
It was found that H37Rv and MDR-MTB were the 2 strains of Mycobacterium tuberculosis against which the benzothiazole analogs were tested. MDR is multidrug-resistant M.tuberculosis which is resistant to isoniazid, rifampicin, and ethambutol. The testing was done by the Agar method.

{2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone

Bhusari KP et al. prepared and reported that {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone was the compound that displayed impressive activity against H37Rv and MDR-MTB with minimum inhibitory concentrations.

Antiviral activity:
Due to vigorous in-silico virtual and HTS which resulted in higher hit-to-lead momentum the anti-viral potential of benzothiazole derivatives were discovered. New series of Iamvudine prodrugs involving N4-substitution with Isatin derivatives showed in-vitro antiretroviral activities.

Anti-malarial activity:
According to Structure-activity relationship studies, nitrogen and sulfur substituted five-membered aromatic ring present within benzothiazole hydrazones might be responsible for their antimalarial activity.
Hout S et al. also reported that tests on the strains W2 and 3D7 of P. falciparum for Antimalarial activity of 2-substituted-6-nitro, 6-amino benzothiazoles, and their anthranilic acids were positive and the results revealed the potency of compounds as the antimalarial agents of clinical and biological research.

Anti- Inflammatory activity:

2-amino-benzothiazole

According to the literature survey, 2-amino-benzothiazole is a versatile compound and could be a potential pharmacophore in safe anti-inflammatory agents. It was noted that when the 2- amino benzothiazole is substituted at 4 or 5 positions with electron-withdrawing groups like Cl, NO2, OCH3, an increase in anti inflammatory activity was found.
Antileishmanial activity:

Anti leishmanial activity

Delmas et al.8 synthesized (1,3-Benzothiazole-2-yl)amino-9-(10H)-acridinone derivatives via a procedure based on the Ullman reaction.

Anti- Convulsant activity :

Amir et al. reported a new series of N-(6-chlorobenzothiazol-2-yl)-2-substituted-acetamide and N-(6-chlorobenzothiazol-2-yl)-2-(substituted-benzylidene)hydrazine-carbothioamides.
Kumar et al. have designed and synthesized a series of 2-[2-(substituted)hydrazinyl]-1,3-benzothiazole and 2-(1,3-benzothiazol-2-yl sulfanyl)-N-(substituted) acetohydrazide.The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test.

Conclusion:
The current survey features the utilization of benzothiazole moiety as a format for the improvement of fresher restorative specialists. Organic properties of the core incorporate anticancer, antidiabetic, pain-relieving, calming, and antimicrobial. With legitimate planning and structure-movement relationship investigations of known benzothiazole, forthcoming mixes can be planned and combined for an assortment of organic exercises.

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