Regional chemotherapy for malignant melanoma

Hafström, L; Mattsson, Jan

doi:10.1016/0305-7372(93)90024-l

Cited by 18 publications

(4 citation statements)

References 36 publications

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“…(A) UV spectral scan of 1 mM benzenesulfinic acid (sodium salt) in buffer vs buffer alone. (B) UV spectral scan of fully decomposed 0.5 mM l,2-bis(phenylsulfonyl)-l-methylhydrazine (added as 5 /ilVmL of a 100 mM solution in DMSO) in buffer vs buffer containing 5 /iL/mL of DMSO. (C) UV spectral scan of 1 mM benzenesulfonic acid (sodium salt) in buffer vs buffer alone.…”

Section: Resultsmentioning

confidence: 99%

Studies on the Mechanism of Decomposition and Structural Factors Affecting the Aqueous Stability of 1,2-Bis(sulfonyl)-1-alkylhydrazines

Penketh¹,

Shyam²,

Sartorelli³

1994

J. Med. Chem.

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1,2-Bis(sulfonyl)-1-alkylhydrazines are highly active experimental antineoplastic agents which decompose with first-order kinetics in neutral aqueous solutions. These agents generate approximately 2 mol of the corresponding sulfinate, 1 mol of nitrogen, and 1 mol of the appropriate alcohol, produced as a consequence of the alkylation of water. Increasing the leaving-group ability of the sulfonyl moiety on N-1 shortens the half-life, while the converse happens with N-2 substitutions. Linear Hammett relationships are found for both types of substitutions. The predictable kinetics of decomposition makes these agents potential candidates for use in regional chemotherapy, where compounds with tunable short half-lives may offer some advantage. Prodrugs of extremely short-lived derivatives of this class may also have utility as targeted alkylating agents.

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Section: Resultsmentioning

confidence: 99%

Studies on the Mechanism of Decomposition and Structural Factors Affecting the Aqueous Stability of 1,2-Bis(sulfonyl)-1-alkylhydrazines

Penketh¹,

Shyam²,

Sartorelli³

1994

J. Med. Chem.

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“…Induction of hsps might be a new therapeutic approach for the therapy of chondrosarcomas. This could easily be [3,5,17]. This approach (induction of hsps by heat and transfection) should be tested in vitro to exclude possible counterregulatory eects.…”

Section: Discussionmentioning

confidence: 99%

Heat shock protein 72 expression in chondrosarcoma correlates with differentiation

Trieb

Kohlbeck

Lang

et al. 2000

Journal of Cancer Research and Clinical Oncology

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“…Some of the longer lived BSHs may be directly useful in regional and cavitorial chemotherapy, where a limb, organ, or body cavity is selectively treated with a chemotherapeutic regimen. − A major aim of this type of treatment is to decrease systemic toxicities. Regional chemotherapy requires venous isolation if long-lived chemotherapeutic agents are utilized.…”

Section: Bis(sulfonyl)hydrazines: a Historymentioning

confidence: 99%

“…In addition to spontaneously activating and hypoxia-targeted BSH produgs, BSH classes susceptible to activation by glutathione S -transferases, proteases, and esterases have been synthesized. , Thus, BSHs are readily latentiated as prodrugs by substitution of the N -2 proton and it is likely that other classes of BSH prodrugs will be developed in the future. Furthermore, the short and predictable half-lives (from seconds to minutes) of the unsubstituted BSH moieties may garner them a role in regional cancer therapy − where individual organs or limbs can be treated, while the majority of tissues largely avoid toxicity. In general, BSHs with short half-lives are excellent for targeting because of two reasons: (a) limited spread from the site of release and (b) protection afforded by MGMT to normal cells by combating low level systemic activation or leakage.…”

Section: Summary Conclusion and Perspectivesmentioning

confidence: 99%

Antitumor Sulfonylhydrazines: Design, Structure–Activity Relationships, Resistance Mechanisms, and Strategies for Improving Therapeutic Utility

et al. 2015

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1,2-Bis(sulfonyl)-1-alkylhydrazines (BSHs) were conceived as more specific DNA guanine O-6 methylating and chloroethylating agents lacking many of the undesirable toxicophores contained in antitumor nitrosoureas. O(6)-Alkylguanine-DNA alkyltransferase (MGMT) is the sole repair protein for O(6)-alkylguanine lesions in DNA and has been reported to be absent in 5-20% of most tumor types. Many BSHs exhibit highly selective cytotoxicity toward cells deficient in MGMT activity. The development of clinically useful MGMT assays should permit the identification of tumors with this vulnerability and allow for the preselection of patient subpopulations with a high probability of responding. The BSH system is highly versatile, permitting the synthesis of many prodrug types with the ability to incorporate an additional level of tumor-targeting due to preferential activation by tumor cells. Furthermore, it may be possible to expand the spectrum of activity of these agents to include tumors with MGMT activity by combining them with tumor-targeted MGMT inhibitors.

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Regional chemotherapy for malignant melanoma

Cited by 18 publications

References 36 publications

Studies on the Mechanism of Decomposition and Structural Factors Affecting the Aqueous Stability of 1,2-Bis(sulfonyl)-1-alkylhydrazines

Studies on the Mechanism of Decomposition and Structural Factors Affecting the Aqueous Stability of 1,2-Bis(sulfonyl)-1-alkylhydrazines

Heat shock protein 72 expression in chondrosarcoma correlates with differentiation

Antitumor Sulfonylhydrazines: Design, Structure–Activity Relationships, Resistance Mechanisms, and Strategies for Improving Therapeutic Utility

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