2-(Alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides: a new class of cancerostatic and antibacterial drugs

Abstract

Organylthiochloracetylenes RSC ≡ CCl (I) exhibit a high reactivity and a great synthetic potential. They represent promising syntones for a targeted synthesis of various S -[1-3]; S,Se -; S,P - [4,5], and N,S -containing acyclic and heterocyclic compounds [6][7][8][9][10]. Esters and alkanammonium salts of organylsulfanylacetic acids, which may be easily obtained on the basis of organylthiochloracetylenes, have already manifested themselves as biologically active compounds with antiagregational, cancerostatic, protective, and adaptive properties [11,12]. New convenient approaches to the synthesis of stable N -(organylthioethynyl)trialkylammonium chlorides have been developed. It was shown that all of them exhibit a broad spectrum of antibacterial activity and a strong antitumor effect both in vitro and in vivo (growth of tumors was suppressed by 82-100%) [13].Developing this new direction in chemistry of polyfunctional derivatives of acetylenes, we studied the reactivity of organylthiochloracetylenes with respect to anionic N -, O -, S -, and Se -nucleophiles; unchanged N -, P -, and S -nucleophiles; and bifunctional N,N -, N,O -, N,S -, and O,S -nucleophiles. In the course of these studies, we developed a convenient method of synthesis of 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides with an yield of 90-96% and studied their structure [14]. Organylthiochloracetylenes readily react with N -(2-hydroxyethyl)-N,N -(dialkyl)amines in a diethyl ether medium at 20-22 ° C to form 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II). The reaction apparently involves intermediate formation of quaternary in ammonium salts, which were recorded by IR spectroscopy:HO R = C 2 H 5 , R 1 = R 2 = CH 3 (IIa); R = Ì -C 4 H 9 , R 1 = R 2 = CH 3 (IIb); R = Ì -C 4 H 9 , R 1 = R 2 = C 2 H 5 (IIc); R = Ì -C 3 H 7 , R 1 = R 2 = CH 3 (IId); R = C 6 H 5 , R 1 = R 2 = CH 3 (IIe); R = C 2 H 5 , R 1 = CH 3 , R 2 = ë 2 ç 4 éç (IIf); R = Ì -C 3 H 7 , R 1 = CH 3 , R 2 = ë 2 ç 4 éç (IIg); R = R 1 = R 2 = C 2 H 5 (IIh); R = iso -C 4 H 9 , R 1 = R 2 = C 2 H 5 (IIi); R = C 2 H 5 , R 1 = C 4 H 9 , R 2 = ë 2 ç 4 éç (IIj).The 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II) synthesized represented white crystalline hygroscopic compounds, stable when stored in the absence of moist and soluble in water and alcohols. The simplicity of synthesis and high yields (90-98%) allow this reaction to be proposed as a convenient preparative way of obtaining these compounds.Compounds (II) contain pharmacophore groups (the quaternary nitrogen atom, sulfur atom, and the oxazolidinium cycle) and are of interest as potential biologically active compounds. We studied the toxicity, cancerostatic, and antibacterial activity of 2-(alkylthiomethylene)-3,3-dialkyl-1,3-oxazolidinium chlorides (II). The existence of cancerostatic and antibacterial activity of chlorides (II) was not obvious, because data on similar compounds exhibiting antitumor or antimicrobial activity are absent in the literature.Fighting against infectious a...

Direct Synthesis of N,N-Dimethyloxazolidinium Chloride by Chloromethylation of 2-(Dimethylamino)ethanol

“…These compounds can also be interesting for the design of novel power cells. Furthermore, oxazolidinium salts exhibit antibacterial and antitumor activity [5]; they also possess surface active properties and are used as detergents, emulsifiers, and flotation agents, as well as for the treat ment of fabrics. The goal of the present work was to develop efficient methods for the synthesis of N-alkyl oxazolidinium salts.…”