Bis-cations with two 2,3-diferrocenylcyclopropenium fragments stabilized with diamino-alkanes: Synthesis and cytotoxic activity

Abstract

Bis-cations with two 2,3-diferrocenylcyclopropenium fragments 3a-d, and the cis-2-(1,2-diferrocenylvinyl)-2-imidazolinium tetrafluoroborates 4a, d or the cis-2-(1,2-diferrocenylvinyl)-3,4,5,6-tetrahydropyrimidin-2-ium tetrafluoroborates 4b, c were obtained by interactions of 2,3-diferrocenyl-1-ethoxycyclopropenium tetrafluoroborate 1 with bis-1,4-N,N-(2a, d) or bis-1,5-N,N-(2b, c) nucleophiles. The reactions of 3a-d with sodium azide proceed with high regioselectivity, forming tetraferrocenyl-substituted compounds: N,N'-bis-(4',6'-diferrocenyl-1',2',3'-triazin-5'-yl)-piperazine 5a, N,N'-bis-(4',6'-diferrocenyl-1',2',3'-triazin-5'-yl)-N,N'-dialkyl-1,3- or 1,2-alkanediamines 5b-d. Sodium hydrogencyanamide reacts with 3a-d to form N,N'-bis-(1'-aza-1'-cyano-3',4'-diferrocenyl-1',3'-butadien-2'-yl)-piperazine 6a, N,N'-dialkyl-1,3- or 1,2-alkanediamines 6b-d and N-(1'-cyano-3',4'-diferrocenyl-1'-aza-1',3'-butadien-2'-yl)-N,N'-dialkyl-alkanediamines 7a-d. The characterization of new compounds was done by IR, ¹H and ¹³C NMR spectroscopy, mass-spectrometry, elemental analysis, and X-ray diffraction analysis only for the compounds 4b, 4d, and 7a. The biological activity of compounds 5a, 6a, 6b, 6c was assessed regarding anticancer activity against U-251, K-562, SKLU-1, HCT-15, and MCF-7 cell lines. All tested compounds showed good activity but compounds 6a and 6b had the best anticancer activity against U-251 (human glioblastoma) and SKLU-1 (human lung adenocarcinoma) cultures.