Synthesis of methylglyoxal thiosemicarbazone and its copper-containing complex possessing DNA-inhibiting and antitumor activity

Abstract

Methylglyoxal thiosemicarbazones are known to possess carcinostatic properties [1,2], but no compounds of this class containing unsubstituted NH 2 group have been reported until now. Direct interaction of methylglyoxal with thiosemicarbazide exhibits variable character and leads to the formation of compounds having different structures, among which monothiosemicarbazone is found in very insignificant amounts [3]. in continuation of the search for new antitumor agents among methylglyoxal thiosemicarbazones, we have studied the hydrolysis of 2-ethoxypropenal thiosernicarbazone obtained previously [4] and the interaction of the resulting methylglyoxal thiosemicarbazone with copper salts.Hydrolysis of 2-ethoxypropenal thiosemicarbazone at pH 2 and a temperature of 50 -60~ proceeds without rupture of the C=N bond and leads to the formation of methylglyoxal thiosemicarbazone (MGTSC): MGTSCAs is known, the carcinostatic properties of thiosemicarbazones increase upon their complexation with transition metals: the complexes are more lipophilic and readily penetrate into cells, possess a greater association constant, and may serve as a base for attaching a cytotoxic ligand [5]. In connection with this, we have studied the formation of complexes between MGTSC and copper(I) chloride (Cu-MGTSC):

Methylglyoxal bis-(N,N-dimethylhydrazone): Synthesis and some reactions

“…The second reaction of these reagents, which is observed in a wet media, is the formation of the hydrazinium salt of the initial diene with maleic acid. The most probable structure of the protonated diene among the four possible forms was revealed by the quantum-chemical calculations of the energy of the molecules and by the analysis of the 13 C NMR chemical shifts.The methylglyoxal bishydrazones, in particular, substituted bisguanylhydrazones and bisthiosemicarbazones, show pronounced biological activity, and some of them are used as drugs [1][2][3][4][5]. Earlier [6] by the reaction of 2-ethoxypropenal with equimolar amount of 1,1-dimethylhydrazine we obtained in a yield of 8% the previously poorly studied methylglyoxal bis-(N,Ndimethylhydrazone) (II) potentially possessing a pharmacological action.…”

“…The methylglyoxal bishydrazones, in particular, substituted bisguanylhydrazones and bisthiosemicarbazones, show pronounced biological activity, and some of them are used as drugs [1][2][3][4][5]. Earlier [6] by the reaction of 2-ethoxypropenal with equimolar amount of 1,1-dimethylhydrazine we obtained in a yield of 8% the previously poorly studied methylglyoxal bis-(N,Ndimethylhydrazone) (II) potentially possessing a pharmacological action.…”