Quinuclidinic Derivatives With Antihistaminic Activity

Silyl modification of biologically active compounds. 12. Silyl group as true incentive to antitumour and antibacterial action of choline and colamine analogues

“…β-Triorganyl-(N,N-dialkylaminoethoxy)silanes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and their methiodides (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), being considered as derivatives of choline, and colamine possessing increased lipophilicity were synthesized by the dehydrocondensation reaction between β-(N,N-dialkylamino)ethanol and triorganylsilanes in the presence of a trace amount of metallic sodium and subsequent reaction with methyl iodide (Scheme 1). The compounds synthesized were characterized by multinuclear NMR data.…”

“…19 Reviewing the families of natural and synthetic antimicrobial drugs, we established that almost all of them contain N-C-C-O-sequence. 20 Indeed this moiety is present in groups of penicilline, cephalosporine, tetracycline, streptomycine and levomycetine antibiotics, in antibiotics of the aminoglycoside, macrolide and polyenene groups, but also in 8-hydroxyquinoline, nitrofuran and quinoxaline containing antimicrobial remedies. 20 Several natural alkaloids (vincristine, vinblastine) and hormonal drugs (tamoxifen) having this sequence are used in medical practice as antitumour drugs.…”

“…20 Indeed this moiety is present in groups of penicilline, cephalosporine, tetracycline, streptomycine and levomycetine antibiotics, in antibiotics of the aminoglycoside, macrolide and polyenene groups, but also in 8-hydroxyquinoline, nitrofuran and quinoxaline containing antimicrobial remedies. 20 Several natural alkaloids (vincristine, vinblastine) and hormonal drugs (tamoxifen) having this sequence are used in medical practice as antitumour drugs. 20 Therefore the aim of this investigation is to study the structure and antitumour and antimicrobial activity relationship by the wide variation of trialkylsilyl substituents at the oxygen atom of different β-ethanolamine derivatives, which can lead to finer selection of prospective compounds for the investigations in vivo.…”

“…20 Several natural alkaloids (vincristine, vinblastine) and hormonal drugs (tamoxifen) having this sequence are used in medical practice as antitumour drugs. 20 Therefore the aim of this investigation is to study the structure and antitumour and antimicrobial activity relationship by the wide variation of trialkylsilyl substituents at the oxygen atom of different β-ethanolamine derivatives, which can lead to finer selection of prospective compounds for the investigations in vivo. Our interest in this research is based on the expectation that such modification or structural restrictions, caused by the presence of positively charged O-organosilicon substituent and positively charged quaternized nitrogen Bioorganometallic Chemistry atom, may influence on the co-ordination behaviour of these compounds in their possible reaction with biological nucleophiles and complex molecules, but also on their adsorptive activities on the cell surface, on permeability of the latter and, as a consequence, on antitumour and antimicrobial properties of β-alkanolamines.…”

“…Between N-methyl (19) and N-ethyl substituted (20) triethylsilylethers, 19 was more effective exhibiting moderate cytotoxic effect concerning mouse hepatoma MG-22A in comparison with inactive 20. In addition, in the group of organosilicon substituted methiodides (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), the more bulky substituted at silicon atom molecules appeared to exert more marked cytotoxic activity. Among possessing cytotoxic properties methiodides (16-18, 21, 23 and 24), the following sequence of the organosilicon substituents in the cytotoxicity display concerning both tumour cell lines has been revealed: Dc 2 Me > EtBu 2 > (C 16…”