Authors:
Daniel I. Hădărugă, Nicoleta G. Hădărugă
Volume 27, Issue 3;
Pages: 335-341; 2021
ISSN: 2069-0053 (print) (former ISSN: 1453-1399), Agroprint;
ISSN (online): 2068-9551
The goal of the study was to evaluate the structural characteristics of some lupanine and cytisine derivatives against various viruses, i.e. influenza A virus subtype H1N1 (AH1N1), human parainfluenza virus type 3 (hPIV3) and the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which determined the coronavirus disease 2019 pandemic (COVID-19). The molecular modelling, conformational analysis, quantitative structure-activity relationships (QSAR) and molecular docking techniques have been used. Nine lupanine or cytisine derivatives and two reference antivirals were studied by molecular modelling and conformational analysis using MM+ molecular mechanics. A wide range of molecular descriptors were calculated for the most stable conformers using QSAR Properties and PaDEL Descriptor software. QSAR models with good statistical parameters were obtained for the largest absolute eigenvalue of Burden modified matrix - n6 / weighted by relative Sanderson electronegativities (SpMax6_Bhe, correlation coefficient, r = 0.62) in the case of AH1N1 and for the information content index - neighborhood symmetry of 4-order (IC4, r = 0.65) in the case of hPIV3. The most active lupanine or cytisine derivative, (1R,5R)-9,11-dibromo-8-oxo-N-phenyl-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-3(4H)-carboxamide, having pIC50 = 4.52 against AH1N1 (antiviral activity close to the reference compound ribavirin, pIC50 = 4.51), was evaluated for its interaction capacity with AH1N1 and SARS-CoV-2 polymerase or protease. In both cases, the calculated interaction energies were favorable, indicating the possible increasing the antiviral activities by structural focusing on new quinolizidine based derivatives.
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