Biopolym. Cell. 2003; 19(3):281-286.
Bioorganic Chemistry
Composite bioregulators on the base of phenazine-1-carboxilic acid and 6-azauracil derivatives. Synthesis and structural characteristics
1Palchykovs'ka L. H., 1Platonov M. O., 1Alexeeva I. V., 1Shved A. D.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


On the base of phenazine-1-carboxilic acid and 6-azauracil derivatives a number of composites have been constructed and synthesized. The structure of above mentioned compounds have been confirmed by UV and H NMR spectra. The functionally important features of these composites structure have been established by nonempirical (ab initio) quantum-chemical conformation analysis at the level of HF/6-31G* theory. It has been revealed that the length, position and composition of the domain connecting linkers influence the formation of compact or loosened «folding» structure of newly synthesized compounds. These two types of structure affect the polymerase complex in a different manner.


[1] Pommier Y, Pourquier P, Fan Y, Strumberg D. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. Biochim Biophys Acta. 1998;1400(1-3):83-105.
[2] Atwell GJ, Rewcastle GW, Baguley BC, Denny WA. Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide. J Med Chem. 1987;30(4):664-9.
[3] Riou JF, Foss? P, Nguyen CH, Larsen AK, Bissery MC, Grondard L, Saucier JM, Bisagni E, Lavelle F. Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Cancer Res. 1993;53(24):5987-93.
[4] Kiprianova EA, Rabionvich AS. [Production of phenazine-1-carboxylic acid by Pseudomonas fluorescens]. Mikrobiologiia. 1969;38(2):224-7.
[5] Brisbane PG, Janik LJ, Tate ME, Warren RF. Revised structure for the phenazine antibiotic from Pseudomonas fluorescens 2-79 (NRRL B-15132). Antimicrob Agents Chemother. 1987;31(12):1967-71.
[6] Sidorik OA, Shevchenko II. Influence of phenazine-1 derivatives of the carboxylic acids on certain types of experimental tumors. Fiziol. active substances. Kiev: Naukova Dumka, 1974;6:92-6.
[7] Rewcastle GW, Denny WA, Baguley BC. Potential antitumor agents. 51. Synthesis and antitumor activity of substituted phenazine-1-carboxamides. J Med Chem. 1987;30(5):843-51.
[8] Preobrazhenskaya MN, Melnik SYa. Nucleic acid analogs - inhibitors of nucleic acid metabolism. M.: VINITI, (Itogi Nauki i Tekhniki Ser Bioorg Khim, vol 1) 1983;59-64.
[9] Mokrushin VS, Pushkareva ZV, Pashkevich TK, Rysakova EN. Synthesis and properties of quaternary salts of derivatives of 1-phenazinegarboxylic acid. Pharmaceutical Chemistry Journal. 1969;3(8):455–7.
[10] Alexeeva I, Palchikovskaya L, Shalamay A, Nosach L, Zhovnovataya V, Povnitsa O, Dyachenko N. N4-amino-acid derivatives of 6-azacytidine: structure-activity relationship. Acta Biochim Pol. 2000;47(1):95-101.
[11] Cristescu C, Marcus I. Derivate des 3,5-dihydroxy-l,2,4-triazins( 6-azauracils) mit mutmalicher cytostatischer Wirkung. Pharmazie. 1961; 16(3): 135-1.
[12] Vicker N, Burgess L, Chuckowree IS, Dodd R, Folkes AJ, Hardick DJ, et al. Novel Angular Benzophenazines: Dual Topoisomerase I and Topoisomerase II Inhibitors as Potential Anticancer Agents. J Med Chem. 2002;45(3):721–39.
[13] Saenger W. Principles of nucleic acid structure. New York: Springer, 1984; 556 p.
[14] Palchikovskaya LI, Platonov MO, Burjanovsky LI, Alexeeva IV, Shved AD. New 6-azapyrimidine derivatives as nonnucleoside inhibitors (NNI's) of nucleic acid biosynthesis: modeling, synthesis and biological activity. Abstr. book of 8 th Int Symp Mol Aspects of Chemother. Gdansk, 2001: 154.
[15] Schmidt MW, Baldridge KK, Boatz JA, Elbert ST, Gordon MS, Jensen JH, et al. General atomic and molecular electronic structure system. J Comp Chem. 1993;14(11):1347–63.