Antiradiation Compounds XXII. Methyl 3-Amino-2-phenyldithiopropenoates and 1,1-Bis(methylthio)-3-amino-2-phenyl-1-propenes

Foye, William O.; Jones, Robert W.; Ghoshal, P. K.

doi:10.1002/jps.2600761012

Cited by 3 publications

(1 citation statement)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1,2-dithiol-3-thiones and dithioesters shown in Table I were synthesised by the general method reported earlier (Foye et al, 1987). Details of the chemistry of these compounds will be published later.…”

Section: Materials and Methods Drugsmentioning

confidence: 99%

1,2-Dithiol-3-thione and dithioester analogues: potential radioprotectors

Teicher

Stemwedel²,

Herman³

et al. 1990

Br J Cancer

View full text Add to dashboard Cite

Summary Several 1,2-dithiol-3-thione and dithioester compounds were assayed for radioprotective capabilities in EMT6 cells in vitro. The 1,2-dithiol-3-thiones were generally more cytotoxic than the dithioesters and in some instances were more cytotoxic toward hypoxic cells than toward normally oxygenated cells. When the drugs were present at a concentration of 50011M for 1 h prior to and during radiation delivery, the 5-(2-thienyl)-1,2-dithiol-3-thione produced a radiation protection factor (RPF) of 2.7 at 1 log of cell kill. The 4-methyl analogue of this same compound was, however, much less effective, producing a RPF of only 1.2. The 4-ethoxycarbonyl analogue was moderately active, producing a RPF of 1.7. The 4-methyl-5-(2-pyrazinyl)-1,2-dithiol-3-thione (Oltipraz) was least effective, yielding a RPF of only 1.1. Of the dithioesters tested, methyl 3-pyrrolidino-2-phenylpropene dithiocarboxylate produced a RPF of 2.6, methyl 3-piperidino-2-phenylpropenedithiocarboxylate a RPF of 2.7, and the corresponding 3-morpholino and 3-thiomorpholino derivatives RPF values of 2.7 and 2.9, respectively. The iodide salt of 4-ethoxycarbonyl-5-(2-thienyl)-1,2-dithiol-3-thione produced a RPF of 2.6 Methyl 3-cyclohexylamino-2-phenylpropenedithiocarboxylate was equally effective (RPF = 2.6). Finally, methyl 3-morpholino-3-thienyl-2-methylpropenedithiocarboxylate and methyl 3-morpholino-3-(2-pyrazinyl)-2-methylpropenedithiocarboxylate were less effective, producing RPF values of 2.0 and 1.6, respectively. These results demonstrate that several of these compounds are highly effective radioprotectors. In vitro and in vivo studies testing their efficacy are underway.

show abstract

Section: Materials and Methods Drugsmentioning

confidence: 99%

1,2-Dithiol-3-thione and dithioester analogues: potential radioprotectors

Teicher

Stemwedel²,

Herman³

et al. 1990

Br J Cancer

View full text Add to dashboard Cite

show abstract

Radiosensitizers and Radioprotective Agents

Bump¹,

Hoffman²,

Foye

2003

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. An important potential use for these agents is to modify the outcome of radiation therapy. Potential radioprotectors or radiosensitizers are organized in this review according to mechanism of action. Most of the agents studied are believed to act by reacting with DNA radicals that are produced within milliseconds of exposure to ionizing radiation. According to this mechanism, protectors restore a single electron to electron‐deficient radicals, preventing degradation of the structure of DNA, whereas sensitizers, such as molecular oxygen or nitroimidazoles, form adducts with these radicals, resulting in damage fixation. WR2721 (Ethyol) is the best‐characterized chemical radioprotector. Preferential activation of WR2721 in certain normal tissues by removal of a phosphate group provides a rationale for selective protection of these tissues. Cytokines and biological modifiers represent an important emerging class of radioprotectors that may be particularly useful in modifying bone marrow injury. Nitroimidazoles have been the most widely studied chemical radiosensitizers. Although clinical results with nitroimidazoles have not been impressive, the potential for this approach has not been fully explored, given that the doses that can be administered have been limited by drug toxicity and supplemental strategies, such as concurrent depletion of endogenous protectors, have not been explored in the clinic. Modifiers of tumor oxygenation represent an important class of radiosensitizers that are currently generating considerable clinical interest. RSR13, a modifier of the oxygen affinity of hemoglobin, is highlighted as an example of the process of drug development for this type of agent.

show abstract

Ring opening–ring closure of 4-phenyl-1,2-dithiole-3-thione: convenient route to novel thiinethione derivatives by the reaction with active methylene nitriles

Barsy

Rady

2010

Journal of Sulfur Chemistry

View full text Add to dashboard Cite

Antiradiation Compounds XXII. Methyl 3-Amino-2-phenyldithiopropenoates and 1,1-Bis(methylthio)-3-amino-2-phenyl-1-propenes

Cited by 3 publications

References 6 publications

1,2-Dithiol-3-thione and dithioester analogues: potential radioprotectors

1,2-Dithiol-3-thione and dithioester analogues: potential radioprotectors

Radiosensitizers and Radioprotective Agents

Ring opening–ring closure of 4-phenyl-1,2-dithiole-3-thione: convenient route to novel thiinethione derivatives by the reaction with active methylene nitriles

Contact Info

Product

Resources

About