The Oxime Derivatives of 1-R-1H-Naphtho[2,3-d][1,2,3]triazole-4,9-dione 2-oxides: Synthesis and Properties.

OBJECTIVE: To synthesize a novel chemotype based on the naphthoquinone scaffold with retained cytotoxicity and provisionally low intracellular oxidation potential. BACKGROUND: Derivatives of naphthoquinone, although potent anticancer agents, can exert heart toxicity due to generation of free oxygen species. METHODS: In this study, we modified the scaffold by replacing one carbonyl group with the oxime moiety. Interestingly, only one carbonyl group in 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 2-oxides reacted with hydroxylamine. The spatial structure was determined by X-ray analysis. New compounds were tested for the ability to form stable complexes with double stranded DNA by spectroscopy and molecular docking and to induce death of tumor cell lines and non-malignant counterparts. RESULTS: The resulting 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 4-oxime 2-oxides were further acylated to produce a series of 1-R-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione 4-(O-acyloxime) 2-oxides. Newly synthesized compounds demonstrated a higher (in submicromolar or low micromolar range) cytotoxic potency against human colon and breast adenocarcinoma cell lines than to non-malignant skin fibroblasts. Spectroscopic measurements revealed that, unlike other classes of quinone derivatives, new naphthotriazoledione oxides did not form stable complexes with double stranded DNA regardless of their fitting to the DNA minor groove (as determined by molecular modeling). CONCLUSION: Thus, our chemical modifications yielded a new chemotype with good cytotoxic properties and yet-to-be-identified intracellular target(s).

Oligonucleotide functionalization by a novel alkyne-modified nonnucleosidic reagent obtained by versatile building block chemistry.

A convenient synthetic strategy has been designed to prepare an alkyne-modified synthon for automated DNA synthesis. It is based on the key O-DMTr-protected 4-(2-hydroxyethyl)morpholin-2,3-dione and building blocks obtained by its functionalization by various aliphatic amines. A respective nonnucleosidic phosphoramidite monomer containing a terminal alkyne in the side-chain was synthesized, and corresponding oligothymidylates incorporating the modification in various positions were prepared. The presence of the alkyne group was confirmed by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between the functionalized oligonucleotide and an azide derivative of 7-nitro-2,1,3-benzoxadiazole.

The power flow angle of acoustic waves in thin piezoelectric plates.

The curves of slowness and power flow angle (PFA) of quasi-antisymmetric (A(0)) and quasi-symmetric (S(0)) Lamb waves as well as quasi-shear-horizontal (SH(0)) acoustic waves in thin plates of lithium niobate and potassium niobate of X-,Y-, and Z-cuts for various propagation directions and the influence of electrical shorting of one plate surface on these curves and PFA have been theoretically investigated. It has been found that the group velocity of such waves does not coincide with the phase velocity for the most directions of propagation. It has been also shown that S(0) and SH(0) wave are characterized by record high values of PFA and its change due to electrical shorting of the plate surface in comparison with surface and bulk acoustic waves in the same material. The most interesting results have been verified by experiment. As a whole, the results obtained may be useful for development of various devices for signal processing, for example, electrically controlled acoustic switchers.

New method of change in temperature coefficient delay of acoustic waves in thin piezoelectric plates.

As is well-known, the development of high-effective and thermostable acoustic devices assumes using the acoustic waves with high coefficient of electromechanical coupling (K2) and low temperature coefficient of delay (TCD). At present, it also is well-known that fundamental shear horizontal (SH0) acoustic waves in thin piezoelectric plates possess by significantly more electromechanical coupling compared to surface acoustic waves (SAW) in the same material. However, although the value of TCD of SH0 waves is insignificantly less than for SAW, this is not enough for development of thermostable devices. This paper suggests a new way of decreasing TCD of SH0 waves in piezoelectric plates at a high level of electromechanical coupling. This way assumes to use the structure containing the piezoelectric plate and liquid with the special dependence of permittivity on temperature. Theoretical and experimental investigation showed that, for SH0 wave in YX LiNbO3 plate at hf = 700 m/s (h = plate thickness, f = wave frequency) the presence of butyl acetate can decrease the value of TCD by six times at K2 = 30%. In a whole the obtained results open the wide prospect of using SH0 wave in thin piezoelectric plate for development of high effective and thermo-stable acoustic devices.