Novel 3- [(methyl)bis(5-trialkylsilylfuran-2-yl) silyl]propylamines have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N-allylamines in the presence of the Speier's catalyst. The effects of the structure of the amine and the alkyl substituent at the silicon atom on the cytotoxicity of the compounds have been studied.Heterocyclic amines are important structural fragments in many medicinal preparations [1,2]. Analysis of antitumor substances has shown that the introduction of a heterocyclic amino group leads to an increase in the solubility and the bioavailability of the active substance. This is seen for piperidine in Arzoxifene [3][4][5], Flavopiridol [6], and Perifosine [7-9], for morpholine in Canertinib [10, 11], Gefitinib [12-14], and Mofarotene [15], as well as for thiomorpholine in Prinomastat [16], piperazine in Dasatinib [17] and Imatinib [18, 19], and pyrrolidine in Idoxifene [20, 21].Previous studies have shown that hetarylaminoalkyl(siloxy)silanes which contain an alkyl(siloxy) group at the silicon atom possess antitumor, neurotropic, and bacteriostatic activity [22,23]. 2-(Aminopropyl)-dimethylsilyl-5-trialkylsilyl(germyl)furans also show a high cytotoxicity towards tumor cells [24,25].Bearing in mind literature information, an analysis of the fragments of known drugs, and also the fact that silylation of compounds increase their lipophilicity (and can even change the metabolism of a substance [26,27]) we decided to prepare a novel series of furylamines which contain, in a single molecule, two furan rings, a heterocyclic amine, and several silicon atoms and to study the cytotoxicity of the novel compounds obtained.The starting furylhydrosilanes 1 and 6 were prepared from furan by two consecutive organolithium syntheses (Scheme 1). Then smooth hydrosilylation of allylamines by hydrosilanes 1 and 6 was carried out when heated in the presence of the Speier's catalyst. This resulted in the preparation in good yields of a series of bis(furyl)silylamines 2-5 and 7-10 which contain two or three heterocycles and three silicon atoms in one molecule. The 13C and 29Si NMR data are given in Table 1. The silicon signals at lower fields (-3.5 to -11.0 ppm) are assigned to the silicon absorption in the trimethyl-and triethylsilyl substituents, and this agrees well
New furan and thiophene derivatives of aldimines o-HO-C 6 H 4 N]CHC 4 H 4 X(R) (X ¼ O, S; R ¼ H, SiMe 3 , SiEt 3 , GeMe 3 , GeEt 3 ) were synthesized by condensation of o-aminophenol with the substituted aldehyde precursor. Their structure, electrochemical reduction/oxidation (in CH 3 CN/0.1 M Bu 4 NPF 6 ), frontier orbital energies, and cytotoxicity have been studied. Their electrochemical redox potentials E p show good correlation with the corresponding orbital energies and the difference E p ox e E p red corresponds well to their orbital hardness.These new compounds have a pronounced cytotoxicity toward cancer cells of human fibrosarcoma HT-1080 and mouse hepatoma MG-22A (IC 50 y 1e8 mg ml À1 ) that can be modulated by introducing a Me 3 M substituent into the fifth position of the heterocycle (e.g., IC 50 (Me 3 Si)/IC 50 (H) ! 50). R 3 M-substitution reduces the orbital hardness of the aldimines studied and facilitates oxidation, promoting their oxidative metabolism. The neighboring group effect in the a-Me 3 Si-substituted thiophene derivative favors S-oxidation, which supposedly makes its metabolic mechanism different compared to R 3 Msubstituted furan series (or for M ¼ Ge in the thiophene series). Interestingly, SiMe 3 and GeMe 3 groups in both heterocyclic series (furan and thiophene) cause opposite trends in cytotoxicity, while the silyl group increases it, the germyl group decreases it.
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