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Synthesis of and structural studies on lead(II) cysteamin complexes.

The novel compounds PbCl(2).(SCH(2)CH(2)NH(3)) (1), Pb(SCH(2)CH(2)NH(2))(2).2PbCl(SCH(2)CH(2)NH(2)) (2), and Pb(SCH(2)CH(2)NH(2))(2) (3) were synthesized by reaction of PbO or PbCl(2) with [HSCH(2)CH(2)NH(3)]Cl and NaOH, and were characterized by elemental analysis, IR-, and UV/vis-spectroscopy. Single-crystal X-ray diffraction revealed different coordination modes for the two Pb atoms in 2. The Pb atom in the Pb(SCH(2)CH(2)NH(2))(2) unit forms two covalent Pb-S and two intramolecular dative Pb...N bonds, leading to a pseudo trigonal bipyramidal configuration with a stereochemically active lone pair. The Pb atom in the PbCl(SCH(2)CH(2)NH(2)) unit, the first moiety structurally characterized of the PbCl(SR) type (R = organic group), forms covalent Pb-Cl and Pb-S bonds, an intramolecular dative Pb...N bond, and two intermolecular Pb...S contacts, giving a pseudo octahedral configuration with a stereochemically active lone pair as well. Despite the Pb(SCH(2)CH(2)NH(2))(2) moiety exhibiting C(2) symmetry in 2, and C(1) symmetry in 3, its structural parameters are rather similar in the two compounds. The influence of the Pb...N bond on molecular structure and thermodynamic stability were estimated by means of quantum chemical ab initio methods. Although an analysis of the wave function in terms of natural bond orbitals (NBO) revealed that n(N) and n(p)(S) compete for the empty p-orbital of the Pb(II) atom, the sigma-type n(N)-6p(Pb) interaction is stronger than the pi-type n(p)(S)-6p(Pb) interaction and hence determines the conformation of the compounds.

Cysteamine↗

Synthesis and radioprotective activity of dipeptide cysteamine and cystamine derivatives.

Some N-(dipeptidyl)-S-acetylcysteamine and N,N'-(dipeptidyl)cystamine salt derivatives were synthesized and evaluated as candidate radioprotector agents. Toxicity and radioprotective activity as the dose reduction factor (DRF) were determined in vivo on mice and compared to N-glycyl-S-acetylcysteamine trifluoroacetate. One of the most interesting compounds of this series was N-glycylglycyl-S-acetylcysteamine trifluoroacetate (8).

Animals↗

New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results.

Three chemical pathways were used for the synthesis of four new N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice. Among these compounds, two of them exhibited a greater antitumor activity compared to that of the parent mixture.

Animals↗

Synthesis and radioprotective activity of new cysteamine and cystamine derivatives.

A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting compounds of this series was N-glycyl-S-acetylcysteamine trifluoroacetate (16, I 102). Structure-activity relationships are discussed.

Amifostine↗