Literature DB >> 8576923

Antitumor 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines.

K Shyam1, P G Penketh, R H Loomis, W C Rose, A C Sartorelli.   

Abstract

Several 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydr azi nes were synthesized and primarily evaluated for antitumor activity against the murine L1210 leukemia. All of the compounds tested were capable of producing "cures" of mice bearing this tumor. One of the most active agents of this class, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- 2(-)[[2-chloroethyl)-amino]carbonyl]hydrazine, was further evaluated against a spectrum of transplanted murine and human solid tumors. Pronounced activity was found against all of the tumors including the murine B16F10 melanoma, M109 lung carcinoma, M5076 reticulum cell sarcoma, and the human LX-1 lung carcinoma. The activities observed compared favorably with those of the established antitumor drugs, cyclophosphamide, mitomycin C, and the nitrosoureas, evaluated concomitantly.

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Year:  1996        PMID: 8576923     DOI: 10.1021/jm9505021

Source DB:  PubMed          Journal:  J Med Chem        ISSN: 0022-2623            Impact factor:   7.446


  20 in total

1.  4-nitrobenzyloxycarbonyl derivatives of O(6)-benzylguanine as hypoxia-activated prodrug inhibitors of O(6)-alkylguanine-DNA alkyltransferase (AGT), which produces resistance to agents targeting the O-6 position of DNA guanine.

Authors:  Rui Zhu; Mao-Chin Liu; Mei-Zhen Luo; Philip G Penketh; Raymond P Baumann; Krishnamurthy Shyam; Alan C Sartorelli
Journal:  J Med Chem       Date:  2011-10-17       Impact factor: 7.446

2.  pH-dependent general base catalyzed activation rather than isocyanate liberation may explain the superior anticancer efficacy of laromustine compared to related 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine prodrugs.

Authors:  Philip G Penketh; Richard A Finch; Rachel Sauro; Raymond P Baumann; Elena S Ratner; Krishnamurthy Shyam
Journal:  Chem Biol Drug Des       Date:  2017-07-17       Impact factor: 2.817

3.  1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic cells.

Authors:  Helen A Seow; Philip G Penketh; Krishnamurthy Shyam; Sara Rockwell; Alan C Sartorelli
Journal:  Proc Natl Acad Sci U S A       Date:  2005-06-17       Impact factor: 11.205

4.  Mode of action of the chloroethylating and carbamoylating moieties of the prodrug cloretazine.

Authors:  Kimiko Ishiguro; Helen A Seow; Philip G Penketh; Krishnamurthy Shyam; Alan C Sartorelli
Journal:  Mol Cancer Ther       Date:  2006-04       Impact factor: 6.261

5.  Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors.

Authors:  Sara Rockwell; Yanfeng Liu; Helen A Seow; Kimiko Ishiguro; Raymond P Baumann; Philip G Penketh; Krishnamurthy Shyam; Oluwatoyin M Akintujoye; Peter M Glazer; Alan C Sartorelli
Journal:  Int J Radiat Biol       Date:  2011-12-20       Impact factor: 2.694

6.  Quantitative relationship between guanine O(6)-alkyl lesions produced by Onrigin™ and tumor resistance by O(6)-alkylguanine-DNA alkyltransferase.

Authors:  Kimiko Ishiguro; Yong-Lian Zhu; Krishnamurthy Shyam; Philip G Penketh; Raymond P Baumann; Alan C Sartorelli
Journal:  Biochem Pharmacol       Date:  2010-07-21       Impact factor: 5.858

7.  Pharmacokinetics, mass balance, and tissue distribution of a novel DNA alkylating agent, VNP40101M, in rat.

Authors:  John Mao; Yang Xu; Diana Wu; Bijan Almassain
Journal:  AAPS PharmSci       Date:  2002

8.  Generation of oxygen deficiency in cell culture using a two-enzyme system to evaluate agents targeting hypoxic tumor cells.

Authors:  Raymond P Baumann; Philip G Penketh; Helen A Seow; Krishnamurthy Shyam; Alan C Sartorelli
Journal:  Radiat Res       Date:  2008-11       Impact factor: 2.841

9.  Development of an O(6)-alkylguanine-DNA alkyltransferase assay based on covalent transfer of the benzyl moiety from [benzene-3H]O(6)-benzylguanine to the protein.

Authors:  Kimiko Ishiguro; Krishnamurthy Shyam; Philip G Penketh; Alan C Sartorelli
Journal:  Anal Biochem       Date:  2008-08-20       Impact factor: 3.365

10.  Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M.

Authors:  G Krishna; W F Hodnick; W Lang; X Lin; S Karra; J Mao; B Almassian
Journal:  AAPS PharmSciTech       Date:  2001-08-26       Impact factor: 3.246

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