Biopolymers and cell. 2007; 23 (5): 441 - 447

Search for novel antifungal compounds among arylamides of 1,2,4-triazinyl-6-propanecarboxylic acid

I. V. Alexeeva, L. G. Palchikovskaya, V .G. Kostina, M. O. Platonov, L. V. Pavlenko, N. A. Lysenko, A .D. Shved

Design and synthesis of a set of 1,2,4-triazinyl-6-propanecarboxylic acid arylamides were developed in order to search for new compounds with fungistatic properties on the basis of azapyrimidine derivatives. Carboxamides capable to block transcription were revealed among obtained compounds using T7 RNA-pol model test-system in vitro, and the only derivatives containing halogene-substituent in pharmacophore part showed the inhibitory properties. The model of virtual triple non-productive complex at polymerase catalytic site (inhibitor-enzyme-DNA template) was proposed, illustrating a possible mechanism of inhibitory action of such compounds on RNA synthesis. Preliminary screening of new triazine derivatives revealed their inhibitory action against some kinds of fungi and bacteria.

Keywords: 1,2,4-triazine derivatives, synthesis, suppression of transcription, T7 RNA-pol, antifungal activity.