Biomolecules bearing the S- or SeAsMe2 function: amino acid and steroid derivatives

Abstract

A series of molecules of the type GXAsMe2 have been synthesized in which X is S or Se and G is a moiety such as an amino acid, a di- or tripeptide, or a lipid. The compounds have been characterized by NMR, mass spectroscopy, and elemental analysis. Cysteine was found to react directly with dimethylarsinic acid to yield cystine and S-dimethylarsinocysteine (1). This reaction occurs also with other biomolecules containing thiol groups and raises serious questions concerning the use of cacodylate buffers in the study of enzyme kinetics and in sample preparation for electron microscopy. In the presence of dimethylchloroarsine and diethylamine, homocysteine thiolactone reacts to form both the dipeptide and the S-AsMe2 bond. Results of carcinostatic, bacteriostatic, and fungicidal testing of these compounds are reported. A hypothesis is advanced to explain the observed carcinostatic action of the dimethylarsino group.

Elimination of the antimicrobial action of the organoarsenical cancer therapeutic, 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid, before finished product sterility testing

“…The results presented in this paper indicate that GSAO specifically inhibits the growth of S. aureus . A similar selectivity towards S. aureus has been previously reported for arsenicals . While resistance to arsenic has also been reported in S. aureus , it was believed that this was mediated through the phosphate transport system and so inferred upon arsenate (V) species, not arsenite (III) species as in GSAO.…”

“…A similar selectivity towards S. aureus has been previously reported for arsenicals. [16] While resistance to arsenic has also been reported in S. aureus, [17] it was believed that this was mediated through the phosphate transport system and so inferred upon arsenate (V) species, not arsenite (III) species as in GSAO. The possibility that arsenic-based compounds specifically inhibit S. aureus growth opens up possibilities for new therapeutic opportunities owing to the resistance of these bacteria to conventional antibiotics.…”

Inactivation of Aeromonas hydrophila metallo‐β‐lactamase by cephamycins and moxalactam

“…The reaction of cacodylate with organic thiols is accompanied by the disappearance of the acid function of cacodylate and the SH groups [26]. The reaction between an aqueous solution of dimethlyarsinic acid and cysteine [(CH 3 ) 2 As(O)OH + 3Cys → (CH 3 ) 2 As‐Cys + cystine + H 2 O] has previously been described [27]. Furthermore, interactions between cacodylate and other enzymes have previously been observed [28].…”

Arsenic derivatives in hematologic malignancies: a role beyond acute promyelocytic leukemia?

“…Zingaro et al synthesized a large number of organic arsenic derivatives 20 years ago [60][61][62][63][64][65]. In mice bearing P388 lymphocytic leukemia cells, some compounds exhibited significant % T/C (treated mice vs. control mice survival) of up to 180 and were used at a dose of 200 mg/kg, significantly higher than LD 50 for As 2 O 3 (10 mg/kg), a compound not active in murine P388 leukemia model [66].…”