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Ukr. Bioorg. Acta 2020, Vol. 15, N2, 48-58.

In silico study of biological affinity of nitrogenous bicyclic heterocycles: fragment-to-fragment approach

Yevheniia S. Velihina1, Nataliya V. Obernikhina2*, Stepan G. Pilyo1, Maryna V. Kachaeva1, Oleksiy D. Kachkovsky1, Volodymyr S. Brovarets1

1 V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine
2 O. O. Bogomolets National Medical University, 13 Shevchenko Blvd., Kyiv, 01601, Ukraine
tel.: 380-96-225-7764; e-mail: nataliya.obernikhina@gmail.com

The biological affinity of model aromatic amino acids and heterocycles and their derivatives condensed with pyridine were carried out in silico and are presented in the framework of fragment-to-fragment approach. The presented model describes interaction between pharmacophores and bio-molecules. Scrupulous data analysis shows that expansion of the π-electron system by heterocycles’ annelation the causes the shifting up of high energy levels, while the appearance of new the di-coordinated nitrogen atom is accompanied by decreasing of the donor-acceptor properties. DFT wB97XD/6-31(d,p)/calculations of possible π-complexes of the heterocycles 1-3 with model fragments of aromatic amino acids, which were formed by π-stack interaction, show an increase in the stabilization energy of π-complexes during the moving from phenylalanine to tryptophan. DFT calculation of pharmacophore complexes with model proton-donor amino acid by the hydrogen bonding mechanism ([H-B] complex) shows that stabilization energy (DE) increases from monoheterocycles to their condensed derivatives. The expansion of the π-electron system of compounds 1a-c by the pyridine cycle reduced the stabilization energy of π-complexes and [H-B] complexes in comparison with the expansion of the π-electronic system by introducing phenyl radicals at positions 2 and 5 of the oxazole ring [18].

fragment-to-fragment approach, biological affinity, [Pharm-BioM] complex, π-stacking interaction, hydrogen bonds.

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