L. G. Palchykovska, О. V. Vasylchenko, M. O. Platonov, V. G. Kostina,
N. A. Lysenko, I. V. Alexeeva, D. M. Hovorun, A. D. Shved

Institute of Molecular Biology and Genetics, National Academy
of Sciences of Ukraine, Kyiv,
e-mail: L.Palchykovska@imbg.org.ua

A convenient method of synthesis was develo­ped and two series of N-arylamides of 9-methyl- and 9-methoxyphenazine-1-carboxylic acids were obtained. By the molecular docking method the mode оf the synthesized compounds interaction with catalytic pocket of the RNA polymerase Т7 transcription complex was simulated. Key ligand-receptor intermolecular contacts were identified. They are realized by various types of non-covalent interactions with line of conservative amino acid residues involved in recognition of incoming nucleotide, catalytic act of RNA synthesis as well as in stabilizing the RNA–DNA hybrid at early steps of transcription. In silico data indicate sufficient affinity of ligands for the receptor and allow to predict their ability to inhibit the functioning­ of RNA poly­merase T7 transcription complex that is consistent with preliminary experimental results. Initial testing in a model RNA polymerase T7 transcription system demonstrates significant inhibition of in vitro RNA synthesis by investigated compounds at a concentration of 25 µg/ml (~80 µM).