Biopolym. Cell. 2013; 29(4):324-329.
http://dx.doi.org/10.7124/bc.000826
Reviews
Synthesis and study on biological activity of nitrogen-containing heterocyclic compounds – regulators of enzymes of nucleic acid biosynthesis
1Alexeeva I. V., 1Shved A. D.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

Results of investigations on the development of new regulators of functional activity of nucleic acid biosynthesis enzymes based on polycyclic nitrogen-containing heterosystems are summarized. Computer design and molecular docking in the catalytic site of target enzyme (T7pol) allowed to perform the directed optimization of basic structures. Several series of compounds were obtained and efficient inhibitors of herpes family (simple herpes virus type 2, Epstein-Barr virus), influenza A and hepatitis C viruses were identified, as well as compounds with potent antitumor, antibacterial and antifungal activity. It was established that the use of model test systems based on enzymes participating in nucleic acids synthesis is a promising approach to the primary screening of potential inhibitors in vitro.
Keywords: 6-azacytidine, as-triazinic nucleosides, acridones, phenazines, benzimidazothiazolones, inhibitors
Full text: (PDF, in English) (PDF, in Ukrainian)

References

[1] Alexeeva I., Dyachenko N., Nosach L., Zhovnovataya V., Rybalko S., Lozitskaya R. et al. 6-Azacytidine – compound with wide spectrum of antiviral activity Nucleosides Nucleotides Nucleic Acids 2001 20, N 4–7:1147–1152.
[2] Zarubaev V. V., Slita A. V., Sukhinin V. P., Nosach L. N., Dyachenko N. S., Povnitsa O. Y. et al. Effect of 6-azacytidine on the course of experimental adenoviral infection in newborn Syrian hamsters J. Chemother 2007 19, N 1:44–51.
[3] Zarubaev V. V., Garshinina A. V., Kalinina N. A., Shtro A. A., Belyaevskaya S. V., SlitaA. V. et al. Activity of ingavirin (6-[2(1H-imidazol-4-yl)ethylamino]-5-oxo-hexanoic acid) against human respiratory viruses in vivo experiments Pharmaceuticals 2011 4, N 12:1518–1534.
[4] Dyachenko N., Alexeeva I., Nosach L., Shalamay A., Rybalko S., Palchikovskaya L. et al. The spectrum of antiviral activity of 6azacytidine, which have the prospect for drug development Int. Conf. «New technologies of obtaining and application of biologically active substances» (Alushta, Crimea, Ukraine; May, 20–25 2002): Abstracts book Alushta, 2002:145–146.
[5] Dyachenko N. S., Rybalko S. L., Nosach L. N., Alexeeva I. V., Shalamay A. S. Antiadenoviral and anti-herpes activity of 6-azacytidine 12th Int. Conf. on Antiviral Research (ICAR-99) (Jerusalem, Israel, March 1999): AB Jerusalem, 1999 P 87.
[6] Nosach L. N., Dyachenko N. S., Shalamay A. S., Alekseeva I. V., Kushko L. Ya., Ozvinchuk I. I. et al. Antiadenovirus and immunostimulating action of 6-azacytidine Biopolym. Cell 1996 12, N 1:75–85.
[7] Alexeeva I. V., Palchikovskaya L. I., Nosach L. N., Usenko L. S., Zhovnovataya V. L., Dyachenko N. S. The glycosilic analogues of 6-azacytidine: synthesis and antiviral activity Biopolym. Cell 2004 20, N 5:435–439.
[8] Alexeeva I., Palchykovskaya L., Shalamay A., Nosach L., Zhovnovataya V., Povnitsa O. et al. N4-amino-acid derivatives of 6azacytidine: structure-activity relationship Acta Biochim. Pol 2000 47, N 1:95–101.
[9] Kostina V. G., Alexeeva I. V., Palchykovskaya L. I. Synthesis of novel 2',3'-dideoxy-6-azacytidine derivatives – potential retroviral reproduction inhibitors Biopolym. Cell 2001 17, N 6 P. 560–564.
[10] Dyachenko N. S., Nosach L. N., Povnitsa O. Y., Kuz'min V. E., Artemenko A. G., Lozitskaya R. N. et al. Structure-antiadenoviral activity of nitrogen containing macroheterocycles and their analogues Mikrobiol. Z 2006 68, N 5:69–80.
[11] Zagorodnaya S. D., Nesterova N. V., Golovan' A. V., Alexeeva I. V., Palchykovskaya L. I., Baranova G. V. AntiEBV activity of 6-azacytidine and its derivatives Mikrobiol. Z 2011 73, N 6:41–49.
[12] Palchikovs'ka L. G., Garmanchouk L. V., Alexeeva I. V., Usenko L. S., Shestakova T. S., Solyanik G. I. et al. The N1-glycosilic analogues of 6-aza-cytidine. Cytotoxic effect and influence on transcription in vitro Biopolym. Cell 2005 21, N 5:433–439.
[13] Platonov MO, Hovorun DM, Alexeeva IV, Sudakov OO, Boiko YuV, Pal'chykovs'ka LG. Nonempirical quantum-chemical conformational analysis of 6-azacytidine, a modified nucleoside with a wide spectrum of biological activities. Dopovidi Nats Akad Nauk Ukrainy. 2004;(3):163-9.
[14] Palchykovs'ka L. H., Platonov M. O., Alexeeva I. V., Shved A. D. Composite bioregulators on the base of phenazine-1-carboxylic acid and 6-azauracil derivatives. Synthesis and structural characteristics Biopolym. Cell 2003 19, N 3:281–286.
[15] Alexeeva I. V., Palchykovska L. G., Kostina V. G., Platonov M. O., Pavlenko L. V., Lysenko N. A. et al. Search for novel antifungal compounds among arylamides of 1,2,4-triazinyl-6-propanecarboxylic acid Biopolym. Cell 2007 23, N 5:441–448.
[16] Kostina V. G., Alexeeva I. V., Lysenko N. A., Grigorjeva S. M., Egorov D. P., Rybalko S. L. et al. Novel derivatives of 3-[3,5-dioxo-1,2,4,5-tetrahydro-1,2,4-triazinyl-6]-propionic acid: synthesis and antifungal effect Ukr. Bioorg. Acta 2012 10, N 1 P. 3–8.
[17] De Logu A., Palchykovska L. H., Kostina V. H., Sanna A., Meleddu R., Chisu L. et al. Novel N-aryland N-heteryl phenazine-1carboxamides as potential agents for the treatment of infections sustained by drug-resistant and multidrug-resistant Mycobacterium tuberculosis Int. J. Antimicrob. Agents 2009 33, N 3 P. 223–229.
[18] Palchykovs'ka L. H., Alexeeva I. V., Kostina V. H., Platonov M. O., Negruts’ka V. V., Deriabin O. M. et Al. New amides of phenazine-1-carboxylic acid: antimicrobial activity and structure-activity relationship Ukr. Biokhim. Zh 2008 80, N 3:140–147.
[19] Stankiewicz-Drogon A., Palchykovska L. G., Kostina V.G., Alexeeva I. V., Shved A. D., Boguszewska-Chachulska A. M. New acridone-4-carboxylic acid derivatives as potential inhibitors of Hepatitis C virus infection Bioorg. Med. Chem 2008 16, N 19:8846–8852.
[20] Alexeeva I. V., Palchykovska L. G., Usenko L. S., Kostina V. G. Tricyclic 1,2,4-triazine bearing heterosystem: directed synthesis of new bioactive compounds Biopolym. Cell 2008 24, N 5 P. 406–411.
[21] Palchykovska L. G., Alexeeva I. V., Platonov M. O., Kostenko O. M., Usenko L. S., Negrutska V. V. et al. New 1,2,4-triazine bearing compounds: molecular modeling, synthesis and biotesting Biopolym. Cell 2009 25, N 6:491–499.
[22] Golovan A. V., Nesterova N. V., Zagorodnya S. D., Alexeeva I. V., Palchykovskaya L. I., Usenko L. S. et al. Inhibitors of EpsteinBarr virus reproduction – ribonucleosides of 3-substituted 1,2,4-triazino-[5,6-b]-[1,4]benzothiazines Mikrobiol. Z 2010 72, N 2:36–42.
[23] Palchykovska L. G., Rybalko S. L., Rymar S. Yu., Starosyla D. B., Alexeeva I. V., Shved A. D. Use of the model DNA-containing enzyme systems to search for inhibitors of nucleic acid synthesis in viruses and bacteria Laboratory Diagnostics 2010 N 3 (53):31–37.
[24] Palchykovska L. G., Alexeeva I. V., Negrutska V. V., Kostyuk Yu. K., Indychenko T. M., Kostenko O. M. et al. Inhibition of in vitro transcription by 2-arylidene derivatives of thiazolo[3,2-a]benzimidazol-3(2H)-one Biopolym. Cell 2010 26, N 6:508–511.