Radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine

Journal Article · Tue Apr 01 00:00:00 EDT 1975 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/jm00238a001· OSTI ID:4127620

Hart, Ronald W.; Gibson, Ruth E.; Chapman, J. Donald; Reuvers, Antoon P.; Sinha, Birandra K.; Griffith, Robert K.; Witiak, Donald T.

For purposes of studying stereostructure-activity relationships at the molecular, cellular, and animal levels and probing the mechanism of 2- mercaptoethylamine (MEA) radioprotection we synthesized several conformationally constrained cyclobutyl analogs. The comparative radioprotective properties for MEA, cis- and trans-2-mercaptocyclobutylamine (2), cis- and trans-2- mercaptocyclobutylmethylamine (3), and trans-2-mercaptomethylcyclobutylamine (4) are discussed in terms of their ability to chemically reduce transient free radicals, the formation of single strand breaks in DNA, and protect Chinese hamster cells (in vitro) and mice against the lethal effects of ionizing radiation. The results are interpreted in light of current proposed mechanisms of action for MEA. No correlation exists between ability of these analogs to enhance mice survival times and their ability to protect against the induction of DNA single strand breaks and the inactivation of proliferative capacity of hamster cells growing in vitro. Analysis of two isomers (cis- and trans-3) on the repair of single strand breaks showed both isomers only marginally influenced the rate and did not influence the extent of single strand break rejoining. The results are consistent with a mode of action involving chemical repair of transient radicals and protection against DNA and critical enzymatic sites.

• Research Organization: Ohio State Univ., Columbus
• Sponsoring Organization: USDOE
• NSA Number: NSA-33-009446
• OSTI ID: 4127620
• Journal Information: Journal of Medicinal Chemistry, Journal Name: Journal of Medicinal Chemistry Journal Issue: 4 Vol. 18; ISSN 0022-2623
• Publisher: American Chemical Society (ACS)
• Country of Publication: United States
• Language: English

Related Subjects

*ANIMAL CELLS-- BIOLOGICAL RADIATION EFFECTS
*DNA-- STRAND BREAKS
*MEA-- RADIOSENSITIVITY EFFECTS
*ORGANIC SULFUR COMPOUNDS-- RADIOSENSITIVITY EFFECTS
*STRAND BREAKS-- RADIOINDUCTION
62 RADIOLOGY AND NUCLEAR MEDICINE
CELL PROLIFERATION
GAMMA RADIATION
HAMSTERS
MICE
RADIATION PROTECTION
RADICALS
SURVIVAL TIME