Special Invited Article

Amino substituted nitrogen heterocycle ureas as kinase insert domain containing receptor (KDR) inhibitors: Performance of structureeactivity relationship approaches

Hayriye Yilmaz ^a,b, Natalia Sizochenko ^b,c, Bakhtiyor Rasulev ^b, Andrey Toropov ^d, Yahya Guzel ^e, Viktor Kuz'min ^c, Danuta Leszczynska ^f, Jerzy Leszczynski ^b,*

^a Kayseri Vocational School, Biomedical Devices and Technologies, Erciyes University, 38039, Kayseri, Turkey
^b Interdisciplinary Center for Nanotoxicity, Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, 39217, USA
^c Odessa I.I. Mechnikov National University, Department of Chemistry, Dvoryanskaya Street, 2, 65082, Odessa, Ukraine
^d Laboratory of Environmental Chemistry and Toxicology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156, Via La Masa 19, Milano, Italy
^e Department of Chemistry, Faculty of Science, Erciyes University, 38039, Kayseri, Turkey
^f Department of Civil and Environmental Engineering, Jackson State University, Jackson, MS, 39217, USA

A quantitative structureeactivity relationship (QSAR) study was performed on a set of amino-substituted nitrogen heterocyclic urea derivatives. Two novel approaches were applied: (1) the simplified molecular input-line entry systems (SMILES) based optimal descriptors approach; and (2) the fragment-based simplex representation of molecular structure (SiRMS) approach. Comparison with the classic scheme of building up the model and balance of correlation (BC) for optimal descriptors approach shows that the BC scheme provides more robust predictions than the classic scheme for the considered pIC50 of the heterocyclic urea derivatives. Comparison of the SMILES-based optimal descriptors and SiRMS approaches has confirmed good performance of both techniques in prediction of kinase insert domain containing receptor (KDR) inhibitory activity, expressed as a logarithm of inhibitory concentration (pIC50) of studied compounds.

Keywords: amino-substituted nitrogen, heterocyclic ureas, descriptors, KDR inhibitors, QSAR, SiRMS, SMILES