Synthesis, anticancer activity and docking of some substituted benzothiazoles as tyrosine kinase inhibitors

H.A. Bhuva, S.G. Kini

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, 1H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4'-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity. © 2010 Elsevier Inc.
Original languageEnglish
Pages (from-to)32-37
Number of pages6
JournalJournal of Molecular Graphics and Modelling
Volume29
Issue number1
DOIs
Publication statusPublished - 2010

Fingerprint

Benzothiazoles
tyrosine
Protein-Tyrosine Kinases
inhibitors
Substitution reactions
Assays
substitutes
synthesis
breast
Halogens
Genistein
cancer
Adenosinetriphosphate
Quercetin
nuclei
adenosine triphosphate
Adenosine Triphosphate
Cells
cultured cells
Nuclear magnetic resonance

Cite this

@article{4d9eefdc8888420a94d6d6352fbb0bed,
title = "Synthesis, anticancer activity and docking of some substituted benzothiazoles as tyrosine kinase inhibitors",
abstract = "Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, 1H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4'-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity. {\circledC} 2010 Elsevier Inc.",
author = "H.A. Bhuva and S.G. Kini",
note = "Cited By :49 Export Date: 10 November 2017 CODEN: JMGMF Correspondence Address: Kini, S.G.; Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Madhav Nagar, Manipal 576104, Karnataka, India; email: suvarna.gk@manipal.edu Chemicals/CAS: 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide, 298-93-1; genistein, 446-72-0; protein tyrosine kinase, 80449-02-1; quercetin, 117-39-5; Antineoplastic Agents; Benzothiazoles; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor, 2.7.10.1 References: (2007) UK Cancer Incidence Statistics by Age, , http://en.wikipedia.org/wiki/cancer, Cancer Research UK, J, (Retrieved on 25-6-2007); (2006) Cancer, , http://en.wikipedia.org/wiki/cancer, F, WHO, World Health Organization, (Retrieved on 25-6-2007); (2007) Report Sees 7.6Million Global 2007 Cancer Deaths, , D , American Cancer Society; Kenneth, K.W., Vogelstein, B., Introduction (2002) The Genetic Basis of Human Cancer, p. 5. , McGraw-Hill, Medical Pub. Division, New York; Zwick, E., Bange, J., Ullrich, A., Receptor tyrosine kinase signalling as a target for cancer intervention strategies (2001) Endocr. Relat. Cancer, 8, pp. 161-173; Gullick, W.J., Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers (1991) Br. Med. Bull., 47, pp. 87-98; Yardern, Y., Ullrich, A., Growth factor receptor tyrosine kinases (1988) Annu. Rev. Biochem., 57, pp. 443-478; Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watenabe, S., Itoh, N., Shibuya, M., Fukami, Y., Genistein, a specific inhibitor of tyrosine-specific receptor kinases (1987) J. Biol. Chem., 262, pp. 5592-5595; Graziani, Y., Erikson, E., Erikson, R.L., The effect of quercetin on the phosphorylation activity of the Rous sarcoma virus transforming gene product in vitro and in vivo (1983) Eur. J. Biochem., 135, pp. 583-589; Cushman, M., Nagrathnam, D., Burg, D.L., Geahlem, R.L., Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues (1991) J. Med. Chem., 34, pp. 798-806; Cunningham, B.D.M., Threadgill, M.D., Groundwater, P.W., Dale, I.L., Hickman, J.A., Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases (1992) Anti-Cancer Drug Des., 7, pp. 365-384; Yates, P.C., McCall, C.J., Stevens, M.F.G., Structural studies on benzothiazoles. Crystal and molecular structure of 5,6-dimethoxy-2-(4-methoxyphenyl-benzothiazole and molecular orbital calculations on related compounds (1991) Tetrahedron, 47, pp. 6493-6502; Hori, N., Tsukamoto, G., Imamura, A., Ohashi, M., Saito, T., Yoshino, K., Synthesis and antiarthritic activity of 2-(4-methylphenyl)benzothiazoles (1992) Chem. Pharm. Bull., 40 (9), pp. 2387-2390; Hutchison, I., Chua, M.-S., Browne, H.L., Trapani, V., Bradshaw, T.D., Westwell, A.D., Stevens, M.F.G., Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl) benzothiazoles (2001) J. Med. Chem., 44, pp. 1446-1455; Mossman, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays (1983) J. Immunol. Methods, 65 (1-2), pp. 55-63; Mendelsohn, J., Baselga, J., The EGF receptor family as targets for cancer therapy (2000) Oncogene, 19, pp. 550-6565; (2007), pp. 1-12. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 1-8. , vLife MDS 3.0 Documentation, Tutorial: Protein Complex Optimization; (2007), pp. 17-20. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 9-14. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 2-11. , vLife MDS 3.0 Documentation, Tutorial: Biopredicta_Protein Complex Optimization; Stevens, M.F.G., MacCall, C.J., Lelievald, P., Alexander, P., Richter, A., Donna, D.E., Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2-phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin (1994) J. Med. Chem., 37, pp. 1689-1695",
year = "2010",
doi = "10.1016/j.jmgm.2010.04.003",
language = "English",
volume = "29",
pages = "32--37",
journal = "Journal of Molecular Graphics and Modelling",
issn = "1093-3263",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Synthesis, anticancer activity and docking of some substituted benzothiazoles as tyrosine kinase inhibitors

AU - Bhuva, H.A.

AU - Kini, S.G.

N1 - Cited By :49 Export Date: 10 November 2017 CODEN: JMGMF Correspondence Address: Kini, S.G.; Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Madhav Nagar, Manipal 576104, Karnataka, India; email: suvarna.gk@manipal.edu Chemicals/CAS: 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide, 298-93-1; genistein, 446-72-0; protein tyrosine kinase, 80449-02-1; quercetin, 117-39-5; Antineoplastic Agents; Benzothiazoles; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor, 2.7.10.1 References: (2007) UK Cancer Incidence Statistics by Age, , http://en.wikipedia.org/wiki/cancer, Cancer Research UK, J, (Retrieved on 25-6-2007); (2006) Cancer, , http://en.wikipedia.org/wiki/cancer, F, WHO, World Health Organization, (Retrieved on 25-6-2007); (2007) Report Sees 7.6Million Global 2007 Cancer Deaths, , D , American Cancer Society; Kenneth, K.W., Vogelstein, B., Introduction (2002) The Genetic Basis of Human Cancer, p. 5. , McGraw-Hill, Medical Pub. Division, New York; Zwick, E., Bange, J., Ullrich, A., Receptor tyrosine kinase signalling as a target for cancer intervention strategies (2001) Endocr. Relat. Cancer, 8, pp. 161-173; Gullick, W.J., Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers (1991) Br. Med. Bull., 47, pp. 87-98; Yardern, Y., Ullrich, A., Growth factor receptor tyrosine kinases (1988) Annu. Rev. Biochem., 57, pp. 443-478; Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watenabe, S., Itoh, N., Shibuya, M., Fukami, Y., Genistein, a specific inhibitor of tyrosine-specific receptor kinases (1987) J. Biol. Chem., 262, pp. 5592-5595; Graziani, Y., Erikson, E., Erikson, R.L., The effect of quercetin on the phosphorylation activity of the Rous sarcoma virus transforming gene product in vitro and in vivo (1983) Eur. J. Biochem., 135, pp. 583-589; Cushman, M., Nagrathnam, D., Burg, D.L., Geahlem, R.L., Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues (1991) J. Med. Chem., 34, pp. 798-806; Cunningham, B.D.M., Threadgill, M.D., Groundwater, P.W., Dale, I.L., Hickman, J.A., Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases (1992) Anti-Cancer Drug Des., 7, pp. 365-384; Yates, P.C., McCall, C.J., Stevens, M.F.G., Structural studies on benzothiazoles. Crystal and molecular structure of 5,6-dimethoxy-2-(4-methoxyphenyl-benzothiazole and molecular orbital calculations on related compounds (1991) Tetrahedron, 47, pp. 6493-6502; Hori, N., Tsukamoto, G., Imamura, A., Ohashi, M., Saito, T., Yoshino, K., Synthesis and antiarthritic activity of 2-(4-methylphenyl)benzothiazoles (1992) Chem. Pharm. Bull., 40 (9), pp. 2387-2390; Hutchison, I., Chua, M.-S., Browne, H.L., Trapani, V., Bradshaw, T.D., Westwell, A.D., Stevens, M.F.G., Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl) benzothiazoles (2001) J. Med. Chem., 44, pp. 1446-1455; Mossman, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays (1983) J. Immunol. Methods, 65 (1-2), pp. 55-63; Mendelsohn, J., Baselga, J., The EGF receptor family as targets for cancer therapy (2000) Oncogene, 19, pp. 550-6565; (2007), pp. 1-12. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 1-8. , vLife MDS 3.0 Documentation, Tutorial: Protein Complex Optimization; (2007), pp. 17-20. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 9-14. , vLife MDS 3.0 Documentation, Tutorial: Engine_Build Molecule; (2007), pp. 2-11. , vLife MDS 3.0 Documentation, Tutorial: Biopredicta_Protein Complex Optimization; Stevens, M.F.G., MacCall, C.J., Lelievald, P., Alexander, P., Richter, A., Donna, D.E., Structural studies on bioactive compounds. 23. Synthesis of polyhydroxylated 2-phenylbenzothiazoles and a comparison of their cytotoxicities and pharmacological properties with genistein and quercetin (1994) J. Med. Chem., 37, pp. 1689-1695

PY - 2010

Y1 - 2010

N2 - Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, 1H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4'-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity. © 2010 Elsevier Inc.

AB - Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, 1H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4'-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity. © 2010 Elsevier Inc.

U2 - 10.1016/j.jmgm.2010.04.003

DO - 10.1016/j.jmgm.2010.04.003

M3 - Article

VL - 29

SP - 32

EP - 37

JO - Journal of Molecular Graphics and Modelling

JF - Journal of Molecular Graphics and Modelling

SN - 1093-3263

IS - 1

ER -