Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: A novel class of anticancer agents

S. N. Manjula, N. Malleshappa Noolvi, K. Vipan Parihar, S. A. Manohara Reddy, Vijay Ramani, Andanappa K. Gadad, Gurdial Singh, N. Gopalan Kutty, C. Mallikarjuna Rao

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine (I) with thiophosgene to obtain optically active isothiocyanates (IIa-h) which on condensation with 4-fluoro-3-chloro aniline (III) yielded various optically active thioureas (IVa-h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds (Va-h). The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass and HRMS. The compounds (IVa-h and Va-h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives (IVe, IVf and IVh) were found most effective. In EAC cells the IC50 values for IVe, IVf, IVh and Vg were found in the range of 10-24 μM, whereas in MCF-7 and HeLa cells the IC50 values were observed in the range of 15-30 μM and 33-48 μM, respectively. In alkaline comet assay the compounds (IVe and IVf) showed dose-dependent DNA damaging activity.

Original languageEnglish
Pages (from-to)2923-2929
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number7
DOIs
Publication statusPublished - 07-2009

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Thiourea
Cytotoxicity
Ascites
Antineoplastic Agents
Inhibitory Concentration 50
Nuclear magnetic resonance
Isothiocyanates
Derivatives
Carcinoma
Bromine
Comet Assay
Cyclization
MCF-7 Cells
Chloroform
HeLa Cells
Amines
Condensation
Assays
Cells
Cell Line

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Manjula, S. N. ; Malleshappa Noolvi, N. ; Vipan Parihar, K. ; Manohara Reddy, S. A. ; Ramani, Vijay ; Gadad, Andanappa K. ; Singh, Gurdial ; Gopalan Kutty, N. ; Mallikarjuna Rao, C. / Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives : A novel class of anticancer agents. In: European Journal of Medicinal Chemistry. 2009 ; Vol. 44, No. 7. pp. 2923-2929.
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abstract = "A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine (I) with thiophosgene to obtain optically active isothiocyanates (IIa-h) which on condensation with 4-fluoro-3-chloro aniline (III) yielded various optically active thioureas (IVa-h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds (Va-h). The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass and HRMS. The compounds (IVa-h and Va-h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives (IVe, IVf and IVh) were found most effective. In EAC cells the IC50 values for IVe, IVf, IVh and Vg were found in the range of 10-24 μM, whereas in MCF-7 and HeLa cells the IC50 values were observed in the range of 15-30 μM and 33-48 μM, respectively. In alkaline comet assay the compounds (IVe and IVf) showed dose-dependent DNA damaging activity.",
author = "Manjula, {S. N.} and {Malleshappa Noolvi}, N. and {Vipan Parihar}, K. and {Manohara Reddy}, {S. A.} and Vijay Ramani and Gadad, {Andanappa K.} and Gurdial Singh and {Gopalan Kutty}, N. and {Mallikarjuna Rao}, C.",
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Manjula, SN, Malleshappa Noolvi, N, Vipan Parihar, K, Manohara Reddy, SA, Ramani, V, Gadad, AK, Singh, G, Gopalan Kutty, N & Mallikarjuna Rao, C 2009, 'Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: A novel class of anticancer agents', European Journal of Medicinal Chemistry, vol. 44, no. 7, pp. 2923-2929. https://doi.org/10.1016/j.ejmech.2008.12.002

Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives : A novel class of anticancer agents. / Manjula, S. N.; Malleshappa Noolvi, N.; Vipan Parihar, K.; Manohara Reddy, S. A.; Ramani, Vijay; Gadad, Andanappa K.; Singh, Gurdial; Gopalan Kutty, N.; Mallikarjuna Rao, C.

In: European Journal of Medicinal Chemistry, Vol. 44, No. 7, 07.2009, p. 2923-2929.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives

T2 - A novel class of anticancer agents

AU - Manjula, S. N.

AU - Malleshappa Noolvi, N.

AU - Vipan Parihar, K.

AU - Manohara Reddy, S. A.

AU - Ramani, Vijay

AU - Gadad, Andanappa K.

AU - Singh, Gurdial

AU - Gopalan Kutty, N.

AU - Mallikarjuna Rao, C.

PY - 2009/7

Y1 - 2009/7

N2 - A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine (I) with thiophosgene to obtain optically active isothiocyanates (IIa-h) which on condensation with 4-fluoro-3-chloro aniline (III) yielded various optically active thioureas (IVa-h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds (Va-h). The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass and HRMS. The compounds (IVa-h and Va-h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives (IVe, IVf and IVh) were found most effective. In EAC cells the IC50 values for IVe, IVf, IVh and Vg were found in the range of 10-24 μM, whereas in MCF-7 and HeLa cells the IC50 values were observed in the range of 15-30 μM and 33-48 μM, respectively. In alkaline comet assay the compounds (IVe and IVf) showed dose-dependent DNA damaging activity.

AB - A novel series of optically active 2-aminobenzothiazole derivatives were synthesized by reaction of optically active amine (I) with thiophosgene to obtain optically active isothiocyanates (IIa-h) which on condensation with 4-fluoro-3-chloro aniline (III) yielded various optically active thioureas (IVa-h). Further oxidative cyclisation in the presence of bromine and chloroform yielded title compounds (Va-h). The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass and HRMS. The compounds (IVa-h and Va-h) were evaluated for in vitro cytotoxicity against mouse Ehrlich Ascites Carcinoma (EAC) and two human cancer cell lines (MCF-7 and HeLa). In preliminary MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies the optically active thiourea derivatives (IVe, IVf and IVh) were found most effective. In EAC cells the IC50 values for IVe, IVf, IVh and Vg were found in the range of 10-24 μM, whereas in MCF-7 and HeLa cells the IC50 values were observed in the range of 15-30 μM and 33-48 μM, respectively. In alkaline comet assay the compounds (IVe and IVf) showed dose-dependent DNA damaging activity.

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