New biological properties of tert-butyl cephalosporanate sulfones

Synthesis of penicillin derivatives and study of their cytotoxic properties

“…Also, the desulfurization of 6~t-chloropenicillanate by Raney nickel has been accomplished. For the substances that have been synthesized, a direct relationship has been established between the intensity of their cytotoxic action/n vitro with respect to tumor cells and the influence of these compounds on the intracellutar generation of nitric oxide radicals.Previously, in the example of sulfones of 7c~-chloro-and 7a-methoxycephalosporanates, we had discovered that these compounds are capable of suppressing the in vitro growth of various types of tumor cells; we also observed simultan.eous, intense intracellular generation of nitric oxide radicals [1]. We are now reporting on an analogous study in which the main objects of investigation were 4-heteryldithio-substituted azetidinones, formed by the interaction of heterocyclic thiols with sulfoxides of 6,6-dihydro-and 6ct-chloropenicillanates, as well as products of their cyclization to form the corresponding 213-heterylthiomethyl-and 213-halomethyl-substituted penicillanates.…”

Synthesis and anticancer properties of 7α-chloro-3-methyl-1,1-dioxoceph-3-em-4-carboxylic acid esters

“…The negative side of this phenomenon consists of the probability of displaying undesirable secondary activity, but the positive is the possibility of using it for the targeted development of substances with new biological properties. Such an interpretation of the secondary activity of clavulanic acid ester, which is a specific inhibitor of the bacterial enzyme β-lactamase, in relation to Human Leucocyte Elastase (HLE) enabled the design of anti-inflammatory analogs of cephalosporin [6].We encountered an analogous secondary effect on studying the biological properties of structural analogs of the tert-butyl ester of 7α-chloro-1,1-dioxoceph-3-em-4-carboxylic acid 1 and 2 [7]. …”

“…We encountered an analogous secondary effect on studying the biological properties of structural analogs of the tert-butyl ester of 7α-chloro-1,1-dioxoceph-3-em-4-carboxylic acid 1 and 2 [7].…”

“…We encountered an analogous secondary effect on studying the biological properties of structural analogs of the tert-butyl ester of 7α-chloro-1,1-dioxoceph-3-em-4-carboxylic acid 1 and 2 [7]. According to the data of Table 1 the presence of an acetoxymethyl group in position 3 of the cephem nucleus (in agreement with the data of [6]) provided the high inhibitory effect of compound 1 in relation to Porcine Pancreas Elastase (PPE) and a weak cytotoxic activity in vitro in relation to monolayer tumor cell lines HT-1080 (human fibrosarcoma) and MG-22a (mouse hepatoma).…”

“…In favor of this hypothesis evidence the negative results on testing the cytotoxic properties in vitro of resynthesized compounds 4a,b, and also of the previously obtained structural analogs of cephalosporin 5-7 [7,11,12] with significant differences in the pharmacophore fragment of the molecule. Thus a reduction in the degree of oxidation of the heterocyclic sulfur atom in 4a,b, substitution of chlorine by hydrogen, iodine, or a trisubstituted silyl group in 5a,b, 6a-c, reduction of the double bond in the cephem nucleus and introduction of a chlorine atom at position 3 in compound 7 is accompanied by a significant decline or complete disappearance of the cytotoxic properties of these compounds in relation to cancer cells HT-1080 and MG-22A in comparison with compound 2.…”