Review that structural modification of benzothiazole derivatives have

Topic: EducationResearch
Sample donated:
Last updated: March 11, 2019

Review ArticleDifferent Biological Activities of Substituted 1, 3 Benzothiazole Derivatives.Midhula CC1,*, Akash Marathakam2, Baijika P3, Shadiha Saheed K4Department of Pharmaceutical Chemistry, National College of Pharmacy, Manassery, Kozhikode*Corresponding author:Email: [email protected] nucleus plays a major role in heterocyclic chemistry due to its structural simplicity. A series of benzothiazole and its derivatives have been synthesized by using various methods and evaluated for its biological activity. It remains one of the most widely studied heterocyclic compounds due to its wide range of biological activities such as anticancer, antimicrobial, antifungal, antibacterial, anticonvulsant, anthelmintic, anti-tubercular, anti-inflammatory, antipsychotic and anti-diabetic activities.

Works of the literature revealed that structural modification of benzothiazole derivatives have improved biological activities and increased a great interest in the research field. The present review focuses on substituted 1, 3 benzothiazoles derivatives with potential activities.Keywords: Heterocyclic compounds, Benzothiazole, Biological activities.Introduction Heterocyclic compounds are cyclic compounds containing one or more atom(s) of other elements along with carbon atoms in the ring system. Nitrogen, sulfur, and oxygen are the most typical heteroatoms. They are widely distributed in nature and are vital to our life.1Heterocyclic compounds may be classified into aliphatic or aromatic. The aromatic heterocyclic compounds are those which have a heteroatom in the ring and resemble benzene in some of their properties.

Don't use plagiarized sources.
Get Your Custom Essay on "Review that structural modification of benzothiazole derivatives have..."
For You For Only $13.90/page!

Get custom paper

Benzothiazole is aromatic heterocyclic compound. The basic structure of benzothiazole consists of a benzene ring fused with thiazole. Thiazole is a 5 membered ring system contains both nitrogen and sulfur.

   These two rings together constitute the basic nucleus 1, 3- benzothiazole. The numbering in thiazole starts from sulfur.2 Benzothiazole moiety is an important component of heterocyclic compounds. These compounds possess diverse biological activity such as antimicrobial, antitubercular, antitumor, antimalarial, anticonvulsant, anthelmintic, analgesic and anti-inflammatory activity. Due to their biological and pharmacological properties, they are considered important for the synthesis of the heterocyclic compound.

3  Fig. 1: Chemical structure of 1, 3-benzothiazoleBenzothiazole is a bicyclic ring system with chemical formula C7H5NS (Fig. 1). It is a weak base, having a variety of biological activities and still having great scientific interest in modern days. They are widely found in the field of bioorganic and medicinal chemistry with application in new drug development.4The study of these privileged structures in drug discovery is a rapidly emerging in the field of medicinal chemistry. BIOLOGICAL ACTIVITYAnticancer activity • Eshkil F et al., (2017) synthesized some thiourea derivatives of benzothiazoles and screened for their anticancer activity.

5 (a) R = H (b) R = CH3 (c) R = OCH3 (d) R = OEtFig. 2• Uremis MM et al.,(2017) carried out synthesis, characterization, in vitro antiproliferative and cytotoxicity effects of a new class of 2-((1R, 2S) -2-((E)-4- substituted styryl) cyclooctyl)benzodthiazole derivatives by  the reaction of 10-(4-substituted benzylidene)bicyclo6.2 decan-9-ones with 2- aminothiophenol in the presence of p-TsOH .6 (a) R = 4-F (b) R = 4-CH3 (c) R = 4- OCH3Fig.

3• Belal A et al., (2017) designed, synthesized new benzothiazole/benzoxazole-pyrazole hybrids with potential as COX inhibitors and evaluated for anticancer activity.7 (a) X = O, R = CH3; (b) X  = O, R = C6H5; (c) X = S, R = C6H5; (d) X = O, R = CH2Cl; (e) X = S, R = CH2ClFig. 4 (a) X = O, R = NO2, (b) X = S, R = NO2, (c) X = O, R = Cl, (d) X = S, R = ClFig, 5• Osmaniye D et al.

, (2017) synthesized some novel benzothiazole-thiazolidine derivatives and evaluated its anticancer activity.8 Fig. 6• Shaik TB et al., (2017) synthesized a series of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents and were rationally designed by performing molecular modeling experiments.9 Fig. 7• Dipesh K et al., (2016) reported the synthesis, characterization of some benzothiazole derivatives bearing oxindole moiety and evaluated for their potential anticancer activity.

10 Fig. 8R1 R2 R3 R4CH3 H H CH3CH3 Cl H HCl H H ClCl H Cl ClCl H Cl HTable 1• Abdelgawad MA et al., (2016) synthesized  new series of quinolone derivatives linked to benzothiazole or benzoxazole moieties and evaluated for anti-cancer and anti-oxidant activities.11 Fig. 9X ArO C6H5O 2-OHC6H4O 4-FC6H4O 4-Cl C6H4O 4-N (CH3)2 C6H4O 4-NO2 C6H4S C6H5S 2-OHC6H4S 4-FC6H4S 4-Cl C6H4S 4-N (CH3)2 C6H4S 4-NO2 C6H4Table 2• Prabhu PP et al., (2015) synthesized a novel series of 2-(3-(4-oxo-2-substituted phenyl thiazolidin-3-yl) phenyl) benzod thiazole-6-carboxylic acid derivatives by various benzothiazole Schiff’s bases by reaction with thioglycolic acid. All the synthesized compounds were screened for their in vitro anticancer activity by 3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on human cervical cancer cell line (HeLa) cell lines.

12 R = H, p-Cl, m-F, p-NO2, p-OCH3, p-CH3, p-OHFig. 10Antimicrobial activity• Sharma PC et al., (2017) synthesized a new series of N-(6-methoxybenzodthiazol-2-yl)-2-substituted phenyl-1H-benzdimidazole-1-carbothioamide derivatives  and evaluated for antibacterial, antifungal and antimalarial effects.13 Fig.

11R1 R2 R3 R4H NH2 H HCl H H HH OCH3 OCH3 OCH3H H OCH3 OCH3H H Cl HF H H HH H NH2 HH H NO2 NO2 Table 3• Saraf DV et al., (2017) carried out synthesis, characterization, antibacterial and antifungal studies on metal complexes with Schiff bases of benzothiazole by the reaction of Schiff bases with the Co and Fe metal acetates.14 Fig. 12R1 R2H  H   Table 4• Incerti M et al., (2017) synthesized a series of N?-(halophenylmethylidene)-1,2-benzothiazole-3-acetohydrazides, novel N-2-phenyl-4-oxo-1,3-thiazolidin-3-yl-1,2-benzothiazole-3-carboxamides/ acetamides and evaluated for their antimicrobial activity.15 Fig.13• Verma AK et al.

, (2014) synthesized parent benzothiazole nucleus by para amino acetanilide, then treatment with various substituted aromatic aldehydes to get the corresponding Schiff’s bases followed by the treatment with pthalic anhydride to form 2-(6-acetamidobenzodthiazol-2ylcarbamoyl)benzoic acid. The structures of synthesized compounds were confirmed by various spectroscopic methods such as IR, 1H NMR, and mass spectroscopy and the products were evaluated for their antibacterial activity.16                X = p-chloro, p-methoxy, 3-nitro, p-methyl              Fig. 14                                                                                              Fig. 15 Fig. 16• Sarkar S et al., (2015) synthesized a novel series of azetidinone derivatives from 2, 3, 4 (trisubstituted benzaldehyde)-N-(6, 7 substituted-1, 3-benzothiazol-2-yl) semicarbazone.

All of the synthesized compounds were confirmed by elemental analyses, IR and 1H NMR spectral data. These newly synthesized compounds were screened for their antibacterial activity.17 Fig. 17R R1 R2F Cl 2-CH3F Cl 4-OCH3F H 4-OCH3F H 2-CH3H Cl 4-OCH3H Cl 2-CH3Table 5Anti-fungal activity• Pejchalová M et al.

, (2017) synthesized a new series of 1-(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl- 3-substituted phenyl diamides, structurally evaluated and screened for antifungal activity against a variety of Candida strains.18 Fig. 18• Kukreja S et al.

, (2016) synthesized some novel series of fluorinated 1, 2, 4-triazolo 3, 4-b benzothiazoles and evaluated for antifungal activity.19 Ar = C6H5, 2’Cl-C6H4, 3’Cl-C6H4, 4’Cl-C6H4, 4’F-C6H4, 2’OH-C6H4 , 3’OH-C6H4 4’OH-C6H4, 4’OCH3-C6H4 , 2’NO2-C6H4, 3’NO2-C6H4, 4’NO2-C6H4, 3’OCH3, 4’OCH 3-C6H3, 3’OCH3,4’OH-C6H3 3’OCH2CH3, 4’OH-C 6H3, 4’N(CH3)2-C6H4, 3’OCH3,4’OCH3,5’OCH 3-C6H2 3’OCH3,4’OH,5’OCH ,3-C 6H2 ,C4H3O ,-CH=CH-C6H5Fig. 19• Maddila S et al., (2016) synthesized  a new series of 5-amino-6-(benzodthiazol-2-yl)-2-(2-(substitutedbenzylidene)hydrazinyl)-7-(4-chlorophenyl)pyrido2,3-dpyrimidin-4(3H)-one derivatives. All the newly synthesized compounds were screened for their in vitro antibacterial activity and for antifungal activity.20  R = H, 4-Cl, 2-Cl, 4-CH3, 4-CH3O, 4-F, 4-NO2, 2, 4-(CH3)2, 4-NH2, 4-C2H5, 4-CH (CH3)2Fig. 20Anticonvulsant activity • Siddiqui N et al., (2017) reported the synthesis and docking study of 2-(6-substituted benzodthiazol-2-yl carbamoyl) methyl-1-(4-substituted phenyl) isothiourea derivatives and evaluated its anticonvulsant activity.

21 R & R1 = H, 4-CH3, 4-OCH3, 4-Br, 4-ClFig. 21• Saleh OA et al., (2016) synthesized N-(6-substituted benzod thiazol-2-yl)-2-(4-substituted piperazin-1-yl) acetamides and evaluated for anticonvulsant activity.

22 Fig. 22R1 R2Br C2H5Cl C2H5CH3 C2H5Br CH2C6H5Cl CH2C6H5CH3 CH2C6H5Table 6• Singh R et al., (2014) synthesized a new series of 2-amino-6-substituted benzothiazole by using 4-substituted aniline and potassium thiocyanate in presence of bromine in glacial acetic acid which further treated with various substituted aromatic aldehydes in presence of glacial acetic acid to get the 2-iminobenzothiazole derivatives.

(6-Substituted-benzothiazol-2-yl)-(4-substituted-benzylidene)-amine derivatives obtained from the reactional sequence were injected intraperitoneally into mice and evaluated by the maximal electroshock (MES), neurotoxicity screen using rotarod at the dose of 30 mg/kg.23  R = Cl, F, Br, NO2Fig. 23 R= Cl, N (CH3)2, OCH3, CH3Fig. 24Anti-inflammatory activity• Patil V et al., (2015) synthesized 2-amino-6-methoxy benzothiazole derivative by simple condensation of benzothiazole with chloroethyl acetate and further treated with hydrazine hydrate to obtain hydrazino benzothiazole. The compounds were screened for their anti-inflammatory activity.24                                                                                             Fig.

25• Kharbanda C et al., (2014) synthesized pyrazolines bearing benzothiazole and evaluated for their anti-inflammatory potential using carrageenan-induced paw edema model.25 X = Cl/ Br.,Ar = Fig. 26MISCELLANEOUS • Charehsaz M et al., (2017) carried out Toxicological Evaluation of Benzothiazole Derivatives Carrying Piperazine Ring.26  R = Benzoyl, 2-FluroylFig.

27• Faraji L et al., (2017) synthesized, characterized a series of novel benzimidazole and benzothiazole derivatives bearing a 1, 2, 3-triazole ring system and their acetylcholinesterase inhibitory activity and evaluated for in- vitro acetylcholinesterase (AChE) inhibitory activity.27 Fig. 28• Thakkar SS et al., (2017) reported synthesis, characterization and biological activities of benzothiazole. Invitro antimalarial and antimicrobial activities were studied. The molecules were characterized by IR, Mass, 1 H NMR, 13C NMR and elemental analysis.28 R =3- NO2, 4-Cl, 2-NO2, 3, 4-di Cl, 4-Br, 4-OH, 4-FFig.

29 R1 = O, S, NHFig. 30• Telvekar VN et al., (2012) designed and synthesized a novel series of substituted 2-(2-(4-aryloxybenzylidene) hydrazinyl) benzothiazole derivatives incorporating 2-hydrazinyl benzothiazole and 4-(aryloxy) benzaldehyde using molecular hybridization approach. All the synthesized compounds exhibited promising activity against Mycobacterium tuberculosis H37Rv strains using REMA.29  Fig.

31CONCLUSIONFrom the above literature review concluded that the benzothiazoles and their derivatives have shown a wide spectrum of biological activities. Researchers have been synthesized different derivatives due to its structural simplicity. This benzothiazole moiety has a greater significance of in the area of drug discovery. REFERENCES1. RG I, Marathe RP. Review on literature study of benzothiazole.

International Journal. 2012; 1(4):11-5.2. Yadav PS, Devprakash D, Senthilkumar GP.

Benzothiazole: different methods of synthesis and diverse biological activities. ChemInform. 2011 Oct 4; 42(40):1-7.

3. Gill RK, Rawal RK, Bariwal J. Recent advances in the chemistry and biology of benzothiazoles. Archiv der Pharmazie. 2015 Mar 1; 348(3):155-78.

4. Jena JI. Significance of benzothiazole moiety in the field of cancer.

Int. J. Pharm. Pharm. Sci. 2014; 6(2):16-22.

5. Eshkil F, Eshghi H, Saljooghi AS, Bakavoli M, Rahimizadeh M. Benzothiazole thiourea derivatives as anticancer agents: Design, synthesis, and biological screening. Russian Journal of Bioorganic Chemistry. 2017 Sep 1; 43(5):576-82.

6. Uremis MM, Ya?l?o?lu A?, Budak Y, Ceylan M. Synthesis, characterization, in vitro antiproliferative and cytotoxicity effects of a new class of 2-((1R, 2S)-2-((E)-4-substitutedstyryl) cyclooctyl) benzo d thiazole derivatives. Organic Communications.

2017 Jul 1; 10(3); 190.7. Belal A, Abdelgawad MA.

New benzothiazole/benzoxazole-pyrazole hybrids with potential as COX inhibitors: design, synthesis and anticancer activity evaluation. Research on Chemical Intermediates. 2017 Jul 1; 43(7):3859-72.8. Osmaniye D, Levent S, Ard?ç CM, Atl? O, Ozkay Y, Kaplanc?kl? ZA. Synthesis and anticancer activity of some novel benzothiazole-thiazolidine derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements. 2017 Nov 14:1-8.

9. Shaik TB, Hussaini SA, Nayak VL, Sucharitha ML, Malik MS, Kamal A. Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as antimitotic agents. Bioorganic & Medicinal Chemistry Letters. 2017 Jun 1; 27(11):2549-58.10. Dipesh K, Noolvi MN.

Synthesis, characterization and evaluation of some benzothiazole derivatives bearing oxindole moiety as potential anticancer agents. International Journal of Pharmaceutical Chemistry and Analysis. 2016; 3(3):143-9.11.

Abdelgawad MA, Lamie PF, Ahmed OM. Synthesis of New Quinolone Derivatives Linked to Benzothiazole or Benzoxazole Moieties as Anticancer and Anti-Oxidant Agents. Med Chem (Los Angeles). 2016; 6:652-7.12. Prabhu PP, Panneerselvam T, Shastry CS, Sivakumar A, Pande SS. Synthesis and anticancer evaluation of 2-phenyl thiaolidinone substituted 2-phenyl benzothiazole-6-carboxylic acid derivatives. Journal of Saudi Chemical Society.

2015 Mar 31; 19(2):181-5.13. Sharma PC, Padwal S, Saini A, Bansal K. Synthesis, characterization and antimicrobial evaluation of benzimidazole clubbed benzothiazole derivatives. Chemical Biology Letters. 2017 Feb 27; 4(2):63-8.

14. Saraf DV, Habib SI, Kulkarni PA. Synthesis, characterisation, antibacterial and antifungal studies on metal complexes with Schiff bases of benzothiazole.15. Incerti M, Vicini P, Geronikaki A, Eleftheriou P, Tsagkadouras A, Zoumpoulakis P, Fotakis C, ?iri? A, Glamo?lija J, Sokovi? M.

New N-(2-phenyl-4-oxo-1, 3-thiazolidin-3-yl)-1, 2-benzothiazole-3-carboxamides and acetamides as antimicrobial agents. MedChemComm. 2017; 8(11):2142-54.16. Verma AK, Martin A, Singh AK. Synthesis, characterization and antibacterial activity of benzothiazole derivatives.

IJPRD, 2014; 6 (08): 080; 85.17. Sarkar S, Chauhan R, Dwivedi J. Synthesis and antibacterial activity of some azetidinone derivatives containing 2-amino 6, 7 substituted benzothiazole.

Turk J. harm Sci. 2015 Jan 1; 12(1):39-44.18. Pejchalová M, Havelek R, Královec K, R?ži?ková Z, Pejchal V. Novel derivatives of substituted 6-fluorobenzothiazole diamides: synthesis, antifungal activity and cytotoxicity. Medicinal Chemistry Research.

2017:1-6.19. Kukreja S, Sidhu A, Sharma VK. Synthesized of novel 7-fluoro-3-substituted-1, 2, 4-triazolo 3, 4-b benzothiazoles (FTBs) as potent antifungal agents: molecular docking and in silico evaluation.

Research on Chemical Intermediates. 2016 Dec 1; 42(12):8329-44.20. Maddila S, Gorle S, Seshadri N, Lavanya P, Jonnalagadda SB. Synthesis, antibacterial and antifungal activity of novel benzothiazole pyrimidine derivatives. Arabian Journal of Chemistry. 2016 Sep 30; 9(5):681-7.

21. Siddiqui N, Alam MS, Sahu M, Naim MJ, Yar MS, Alam O. Design, synthesis, anticonvulsant evaluation and docking study of 2-(6-substituted benzo d thiazol-2-ylcarbamoyl) methyl-1-(4-substituted phenyl) isothioureas. Bioorganic Chemistry. 2017 Apr 30; 71:230-43.

22. Saleh OA, El-Behery MF, Aboul-Enein MN, El-Azzouny AA, Maklad YA. Anticonvulsant potential of certain N-(6-substituted benzo d thiazol-2-yl)-2-(4-substituted piperazin-1-yl) acetamides. Egyptian Pharmaceutical Journal. 2016 May 1; 15(2):62.23.

Singh R, Sharma S. Synthesis, characterization and evaluation of 2-imino benzothiazole derivatives as anticonvulsant agents. Int J Pharma Sci Res. 2014 May; 5:213-7.24.

Patil V, Asrondkar A, Bhadane V, Bobade AS, Chowdhary A. Synthesis and Anti-inflammatory activity of 2-amino-6-methoxy benzothiazole derivative. Journal of Applied Chemistry.

2015; 8(1):1-2.25. Kharbanda C, Alam MS, Hamid H, Javed K, Bano S, Dhulap A, Ali Y, Nazreen S, Haider S. Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents. Bioorganic & medicinal chemistry. 2014 Nov 1; 22(21):5804-12.26. Charehsaz M, Gürdal EE, Helvac?o?lu S, Yar?m M.

Toxicological Evaluation of Benzothiazole Derivatives Carrying Piperazine Ring. Marmara Pharmaceutical Journal. 2017 Jan 1; 21(2).27. Faraji L, Shahkarami S, Nadri H, Moradi A, Saeedi M, Foroumadi A, Ramazani A, Haririan I, Ganjali MR, Shafiee A, Khoobi M. Synthesis of novel benzimidazole and benzothiazole derivatives bearing a 1, 2, 3-triazole ring system and their acetylcholinesterase inhibitory activity.

Journal of Chemical Research. 2017 Jan 1; 41(1):30-5.28. Thakkar SS, Thakor P, Ray A, Doshi H, Thakkar VR. Benzothiazole analogues: synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities. Bioorganic & Medicinal Chemistry.

2017 Jul 17.29. Telvekar VN, Bairwa VK, Satardekar K, Bellubi A. Novel 2-(2-(4-aryloxybenzylidene) hydrazinyl) benzothiazole derivatives as anti-tubercular agents. Bioorganic & medicinal chemistry letters. 2012 Jan 1; 22(1):649-52..


Choose your subject


I'm Jessica!

Don't know how to start your paper? Worry no more! Get professional writing assistance from me.

Click here