Anti-mitotic Activity of the Benzothiazole-pyrazole Hybrid Derivatives

Author(s): M. Bhat* , S.L. Belagali , N.K.H. Kumar , S. Jagannath .

Journal Name: Anti-Infective Agents

Volume 17 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Nitrogen-containing heterocyclics are abundant in natural products and also in synthetic drug molecules because of a variety of applications and superior pharmacological profile action. Pyrazoles are the integral architects of many of the heterocyclic compounds with superior biological activity.

Methods: Two series of the pyrazole conjugated Benzothiazole derivatives were synthesized. The pyrazoles were synthesized by the Vilsmeier-Haack reaction and then conjugated with benzothiazole hydrazine and hydrazide by imine bond formation. The synthesized compounds were screened for anti-mitotic activity using Allium assay.

Results: Here, the anti-mitotic activity, the percentage of cell division and the percentage of inhibition compared to the control were calculated. Compound 4b (-OMe), 4c (-OH), 5b (-OMe), 5c (- OH) and 5d (-CH3) had electron donating groups which showed excellent activity, was followed by 4f and 5f where they contain p-Bromo substitution, showing moderate activity.

Conclusion: In the two series, benzothiazole linked to pyrazole through the hydrazide bridging (5a-5i) had superior to hydrazine bridging (4a-4i). The observed chromosomal aberrations are because of the structural morphology and binding sites of the molecule with the chromosome.

Keywords: Pyrazole, benzothiazole, antimitotic activity, ID50 value, hydrazine, chromosome.

[1]
Vijesh, A.M.; Isloor, A.M.; Shetty, P.; Sundershan, S.; Fun, H.K. New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur. J. Med. Chem., 2013, 62, 410-415.
[2]
Ningaiah, S.; Bhadraiah, U.K.; Keshavamurthy, S.; Javarasetty, C. Novel pyrazoline amidoxime and their 1,2,4-oxadiazole analogues: Synthesis and pharmacological screening. Bioorg. Med. Chem. Lett., 2013, 23, 4532-4539.
[3]
Horton, D.A.; Bourne, G.T.; Smythe, M.L. The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem. Rev., 2003, 103, 893-930.
[4]
Paul, S.; Gupta, M.; Gupta, R.; Loupy, A. Microwave assisted solvent-free synthesis of pyrazolo [3,4-b]quinolines and pyrazolo [3,4-c]pyrazoles using p-TsOH. Tetrahedron Lett., 2001, 42, 3827-3829.
[5]
Wentland, M.P.; Aldous, S.C.; Gruett, M.D.; Perni, R.B.; Powles, R.G.; Danz, D.W.; Klingbeil, K.M.; Peverly, A.D.; Robinson, R.G.; Corbett, T.H.; Rake, J.B.; Coughlin, S.A. The antitumor activity of novel pyrazoloquinoline derivatives. Bioorg. Med. Chem. Lett., 1995, 5, 405-410.
[6]
Bhat, M.; Belagali, S.L.; Hemanth, K.N.K.; Mahadev, K.S. Synthesis and characterization of novel benzothiazole amide derivatives and screening as possible antimitotic and antimicrobial agents. Res. Chem. Intermed., 2017, 43, 361-378.
[7]
Schiff, H. Mitteilungen aus dem universitats laboratorium in Pisa: Eineneue reihe organischer basen Justus. Liebigs Ann. Chem., 1864, 1, 118-119.
[8]
Przybylski, P.; Huczynski, A.; Pyta, K.; Brzezinski, B.; Bartl, F. Biological properties of Schiff bases and azo derivatives of phenol. Curr. Org. Chem., 2009, 13, 124-148.
[9]
Bhat, M.; Belagali, S.L. Synthesis, characterization and biological screening of pyrazole-conjugated benzothiazole analogs. Future Med. Chem., 2017, 10(1), 71-87.
[10]
Rathelot, P.; Azas, N.; El-Kashef, H.; Delmas, F.; C. Di Giorgio, ; Timon-David, P.; Maldonado, J.; Vanelle, P. 1,3-Diphenylpyra-zoles: Synthesis and antiparasitic activities of azomethine derivatives. Eur. J. Med. Chem., 2002, 37, 671-679.
[11]
Fissceja, G. The Allium test as a standard in environmental monitoring. Hereditas, 1985, 102, 99-112.
[12]
Levan, A. Die Zytologie von Allium Cepa X fistulosum. Heriditas, 1938, 24, 471-486.
[13]
Rekha, K.; Kak, S.N.; Langer, A. Cytological abnormalities in Artemisia pollens Wall. Induced by gamma rays. Ind. J. Fores, 2004, 27, 355-359.
[14]
Grant, W.F. Chromosome Aberration in plants as monitoring system. Environ. Health Perspect., 1978, 27, 37-43.
[15]
Umesha, B. Sowbhagya; Vinaya; Basavaraju, B. Synthesis and evaluation of antimitotic activity of N-phenyl tetralones. J. Appl. Pharm. Sci., 2018, 8(5), 94-100.
[16]
Sundaresan, K.; Umamatheswari, S.; Tharini, K. Synthesis, characterization and antimitotic activity of cyanoacetyl hydrazone derivatives. Eur. J. Pharm. Med. Res., 2018, 5(5), 314-320.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 1
Year: 2019
Page: [66 - 73]
Pages: 8
DOI: 10.2174/2211352516666180914101758

Article Metrics

PDF: 33
HTML: 1