2-Chloroethyl (methylsulfonyl)methanesulfonate and related (methylsulfonyl)methanesulfonates. Antineoplastic activity in vivo

Yf, Shealy; Ca, Krauth; Wr, Laster

doi:10.1021/jm00371a019

Cited by 18 publications

(4 citation statements)

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“…6 The antitumor activity of the CNUs has been suggested to result from chloroethylation and subsequent crosslinking of DNA. 7 In support of this view is the observation that many chloroethylating agents with no carbamoylating activity (e.g., clomesome 8 ) possess excellent antineoplastic activity. Furthermore, replacement of the chloro group in the CNUs by a hydroxyl group resulted in a considerable drop in antineoplastic activity.…”

mentioning

confidence: 99%

Antitumor 2-(Aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines

et al. 1996

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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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confidence: 99%

Antitumor 2-(Aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines

et al. 1996

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“…These observations suggest that no barriers exist to the distribution and elimation of metronidazole from the tumour. The concentration of clomesone, a novel alkylating agent (Shealy et al 1983, Shealy, Krauth &Laster 1984 appeared to be unrelated to the concentration of lissamine green. At 30 min, the concentration of clomesone in plasma exceeded that found in either the well-or the poorly-perfused regions delineated by the lissamine green.…”

Section: Uniformly Distributed Compoundsmentioning

confidence: 98%

Diversity of penetration of anti‐cancer agents into solid tumours

Simpson-Herren

Noker

1991

Cell Proliferation

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Failure of anti-cancer agents to reach all clonogenic cells at cytotoxic concentrations is recognized as an important form of resistance in solid tumours. Subcutaneously implanted mammary adenocarcinoma 16/C was used to evaluate the intratumour distribution of five alkylating, bioreductive alkylating and intercalating agents and two radiation sensitizers. The agents were classified according to their in vivo distribution in well- and poorly-perfused tumour regions, as delineated by lissamine green. The classifications were: (1) distribution in direct proportion to the vascular supply; (2) uniform distribution to well- and poorly-perfused tumour regions; and (3) preferential retention in the poorly-perfused tumour regions. Our current state of knowledge did not allow reliable prediction of the classification based on chemical structure or mechanism of action.

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“…2-Chloroethyl(methylsulphonyl)methanesulphonate (Clomesone), the most active analogue tested, was shown to be highly effective against P388 leukaemia in vivo (Shealy et al, 1984). The chemical structure of Clomesone is shown in Figure 1.…”

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confidence: 99%

Pre-clinical evaluation of a novel chloroethylating agent, Clomesone

Matthew

Phillips²,

Loadman³

et al. 1993

Br J Cancer

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The in vitro activity of the novel chloroethylating agent, Clomesone, was investigated in a panel of established murine and human tumour cell lines. In vivo anti-tumour activity was examined against three transplantable adenocarcinomas of the mouse colon and in vivo bone marrow toxicity was assessed using a spleen colony forming unit assay. The pharmacokinetic behaviour of the drug in vivo and drug stability in vitro was analysed by gas chromatography with electron capture detection. Clomesone exhibited no activity in vitro against the majority of cell lines derived from solid human colorectal carcinomas. Anti-tumour activity against the murine tumours in vivo was not impressive and was accompanied by myelosuppression. Pharmacokinetic data suggested that the lack of in vivo activity was due to the failure to achieve effective anti-neoplastic drug concentrations at the tumour site. It was concluded that this study found no evidence to suggest that Clomesone was toxicologically more selective than the chloroethylnitrosoureas.

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2-Chloroethyl (methylsulfonyl)methanesulfonate and related (methylsulfonyl)methanesulfonates. Antineoplastic activity in vivo

Cited by 18 publications

References 1 publication

Antitumor 2-(Aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines

Antitumor 2-(Aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- hydrazines

Diversity of penetration of anti‐cancer agents into solid tumours

Pre-clinical evaluation of a novel chloroethylating agent, Clomesone

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