Antiradiation Compounds I
A series of S-acyl derivatives of BETA -mercaptoethylamine (MEA) was prepared in an attempt to provide compounds having protective effects in animal cells against ionizing radiation and having less toxicity than MEA itself. In general, toxicity to animals was reduced and good protective ability against x radiation was retained in some of the esters. The dithiocarbamic acid of MEA was also prepared, but attempts to acyiate the compound, which showed good antiradiation effects at toxic dose levels in mice, gave only decomposition products. The S-acetyl derivative of MEA gave 60% protection over a 30-day survival period when mice were irradiated with 800 r. An 80% survival was observed after a dose of 575 r, nontoxic doses of the compound being inlected 15 min prior to exposure. The S-octanoyl ester gave similar results. The S- myristoyl ester provided 65% protection against a dose of 575 r, but was ineffective against 800 r. The dithiocarbamic acid gave 75% protection against 800 r and 95% protection against 575 r, making this compound almost as effective as MEA itself, The benzoyl ester of MEA was not appreciably effective, affordirg only 10% protection from 800 r. The chloroacetyl ester gave no protection at all. It is possible that the compound underwent polymerization or cyclization before reaching the cells, when neutralized prior to injection. A lowering of toxicity resulted from ester formation. On the basis of the mixed disulfide hypothesis of radiation protection by mercaptans, the S-acyl derivatives of MEA would be expected to undergo hydrolysis in vivo, thus liberating MEA to form mixed disulfides with vital thio groups in the celis. However, rearrangement to the N- acyl derivatives was shown to occur readily at pH's above 7.
- Research Organization:
- Massachusetts Coll. of Pharmacy, Boston
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-17-005924
- OSTI ID:
- 4753315
- Journal Information:
- Journal of Pharmaceutical Sciences, Vol. 51, Issue 2; Other Information: Orig. Receipt Date: 31-DEC-63; ISSN 0022-3549
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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