Ferrocenylalkyl azoles: bioactivity, synthesis, structure

Abstract

aThe toxicity of ferrocenylethyl benzotriazole (1) and other ferrocene compounds including ferrocenylmethyl benzimidazoles (4,5,6,11), ferricenium salts (3,9,10) and ferrocenylmethyl adenine (7), was studied. All ferrocene complexes under investigation showed low or medium toxicities. On the basis of an earlier model of chemical carcinogenesis, the antitumor activity of ferrocenylalkyl azoles 1, 8 and ferricenium salts 9, 10 was studied in vivo in the so-called sub-capsular test on human tumors. This effectiveness was compared with that of cisplatin. A series of ferrocenylalkyl azoles were synthesized by interacting azoles either with α-hydroxyalkyl ferrocenes FcC(OH)R 1 R 2 in organic solvent in the presence of aqueous HBF 4 in quantitative yields or with trimethyl(aminomethyl)ferrocene iodide in an aqueous-basic medium in good yields. The X-ray determinations of molecular and crystal structures of α-(1-benzotriazolyl)ethylferrocene (1) and α-(1-naphthatriazolyl)ethylferrocene (12) were performed.

Synthesis, structure and in vitro cytostatic activity of ferrocene—Cinchona hybrids

“…8 The potential of simple ferrocene-based heterocycles in fighting cancer,ferrocenylalkyl-substituted azoles were also found to exhibit in vivo antitumor activity presenting up to 100% of tumour growth inhibition associated with lower toxicity when compared to clinically used drugs. 9 In this regard, even metalfree organic 1,4-disubstituted 1,2,3-triazoles exhibit significant antiproliferative effect against a wide range of human malignant cell lines. 10 On the other hand, 1,5-disubstituted 1,2,3-triazole analogues of combretastatin A-4 were also found to display marked cytotoxicity on several cancer cell lines.…”

o‐Carboxybenzoylferrocene. Bioactivity and chemical Modifications

“…Carcinoma 755, as noted earlier, [11] is the most sensitive model to the action of the ferrocene compounds in comparison with the other tested tumor systems.…”

“…[3] It was established that the ferrocene compounds should be positively charged in order to display antitumor activity. However, later the antitumor activity of uncharged ferrocene compounds -ferrocenylalkyl azoles, [11,14] ferrocene-modified complexes of platinum(II) [15] and ferroceneconjugates of polyaspartatamides [12] -was shown. The authors [13] believed that these originally uncharged compounds may acquire the charges during their transportation in biological systems (via oxidation to ferricenium salts or protonation of nitrogencontaining heterocyclic moieties).…”

“…[6,13] Thus, positive-charged ferricenium salts with different substituents [3,4,8] -polyferrocenylenemethylene ologomer with ferrocene and ferricenium moieties, [8] bis-(ferrocenylmethyl)imidazolium salt [8] and bis-(ferrocenylalkyl) benzotriazolium salts [8] -in in vivo experiments inhibited tumor growth. It was found that uncharged ferrocene conjugates of polyaspartatamides (in vitro) [12] and ferrocenylethyl benzimidazole (in vivo) [11] demonstrated the inhibition effect as well. Moreover, potentially anionogenic acids such as ferrocenylacetic FcCH 2 COOH and ferrocenylmethylthiomalic FcCH 2 S-CHCOOH-CH 2 COOH in clonogenic in vitro tests inhibited a formation of colonies of cells of human lung cancer and cultures of lung carcinoma PC-9, [6] to even a greater degree than do ferricenium salts.…”

Synthesis, Crystal Structure and Properties of Iodide and Hexafluorophosphate Salts of 2-Ferrocenyl (or Binuclear Ferrocenyl)-1,3-dialkylbenzimidazolium

“…近年来将苯并 咪唑和二茂铁的优良特性结合在同一个分子中的研究 引起了很大的关注. Snegur 等 [12] 合成了一系列含二茂铁 基的苯并咪唑衍生物, 并对它们的抗癌活性进行了研 究. Hamad 等 [13] 合成了 2-二茂铁基苯并咪唑的衍生物, 发现它们有很好的抗真菌效果, 有潜力成为抗真菌药物 的设计平台. Toppare 等 [14] 报道了 2-二茂铁苯并咪唑作 为电子受体单元的电子供体-受体-供体的多聚物的 合成, 对它们的电子传递性能进行了研究.…”