Search

The impact of a number of synthetic nucleoside derivatives on the growth and survival of cultured human ovarian tumor cells (line SKOV-3) and normal human lung fibroblasts was investigated. It was shown that the dialdehyde derivatives of uridine, 1-β-D-eritrofuranozyl uracil and 3'-O-β-D-ribofuranosyl-2'-deoxythymidine, in contrast to their unoxidized counterparts, exert marked toxic effect on SKOV-3 cells. Cultured human fibroblasts were less susceptible to the damaging effect of the dialdehyde nucleosides. The dialdehyde derivative of 1-β-D-eritrofuranozyl uracil demonstrated greatest differences in the cytotoxic effect on these cultures: inhibition of tumor SKOV-3 cells growth on 50% or more was achieved at the concentrations of this compound ten times lower than in the case of normal fibroblasts.

A series of novel non-peptidic furin inhibitors containing amidinohydrazone moieties has been synthesized under interaction of dialdehydes, the derivatives of ethylene diethylvanillin ethers, with aminoguanidine bicarbonate. Two aryl cycles were bridged by 1,2-ethylene-, 1,4-buthylene- or 1,4-dimethylenebenzene-group. The compounds have been found to inhibit furin. The antifurin activity was shown to grow with the increase of the length and/or hydrophobicity of the bridge. The most potent compound, containing in the bridge the lypophylic benzene cycle was found to inhibit the activity of furin with Ki = 0.51 microM.

Oligonucleotides with 1,2-diol grouping were prepared from 2'-O-[2-(2,3-dihydroxypropyl)amino-2-oxo-ethyl]uridine 3'-phosphoramidite. The thermal stability of modified DNA duplexes and their ability to form complexes with the p50 subunit of the NF-kappaB transcription factor and (cytosine-5)-DNA methyltransferase SsoII were studied. The periodate oxidation of the l,2-diol grouping of the oligonucleotides resulted in reactive 2'-aldehyde derivatives. The opportunity of their use for the affinity modification of DNA-recognizing proteins was studied.

Nonsymmetrical aldehyde derivatives of gossypol, a yellow polyphenolic pigment of cottonseed, were synthesized by reactions with ammonia, aniline, 4-aminoantipyrine, and barbituric acid. Their structures were determined by UV spectrophotometry and IR and (1)H NMR spectroscopy methods. Their acute toxicities in white mice were compared with those of gossypol and the corresponding symmetrical analogues. It was demonstrated that in general, the fewer free aldehyde groups that contained the gossypol derivative, the lower its acute toxicity. Only in the case of a nonsymmetrical gossypol derivative bearing a 4-aminoantipyrine residue did we observe a deviation from the above correlation: its symmetrical counterpart was even more toxic, but still less toxic than gossypol.

Various synthetic approaches to modified peptides with the C-terminal aldehyde group, capable of inhibiting a number of proteolytic enzymes belonging to the classes of thiol, serine, and aspartyl proteases, are considered. Both chemical methods, including solid phase peptide synthesis now widely used, and biocatalytic synthetic methods for obtaining these substances are discussed in detail.

The employment of periodate oxidation in the chemistry of nucleic acids and their components is reviewed. The reaction mechanism, structural requirements to substrates, and synthesis of dialdehyde derivatives of nucleosides, nucleotides, and oligonucleotides are discussed in the first part. The second part involves chemical, physicochemical, and biological properties of the dialdehyde derivatives, as well as their use for the affinity modifications of proteins.

Reactions of levorin, a polyenic macrolide antibiotic, with aromatic aldehydes and hypophosphorous acid resulted in formation of its amino phenylphosphonium derivatives. Physicochemical and biological properties of the derivatives were studied. The levorin amino phenylphosphonium derivatives were shown to be low toxic and have antifungal and antiviral activities.