Molecular analysis coupling of some amino-derivatives with WRN exonuclease using a theoretical model

Abstract

Studies indicate that some types of cancer have been associated with Werner syndrome (WR), which is characterized by premature aging. Some WR inhibitors, such as camptothecin, HRO761, VVD-133214, and KWR05, have been used to treat this clinical pathology; however, the interaction of these drugs with some biomolecule related with WR is not clear. For this reason, in this study, the coupling of amino derivatives (compounds 1-25) with WRN exonuclease was determined using 2fbt protein, HOR761, NSC19630, NSC617145, and NCS drugs as theoretical tools in the DockingServer program. Besides, physicochemical parameters, such as HOMO (highest occupied molecular orbital), LUMO (lowest unoccupied molecular orbital), MR (molecular refractivity), and MV (molar volume), involved in the chemical structure of amino derivatives 1-25 were determined. The results showed differences in HOMO-LUMO, MR, and MV values for compounds 1-25. This data suggests that the reactivity of each compound depends on different functional groups involved in their chemical structure. Other data indicate that inhibition constant involved in the coupling of amino derivatives with 2fbt protein for compounds 3 (1.30), 6 (1.20), 7 (1.46), 8 (1.03), 14 (1.04), 15 (1.02), and 21 (2.57) was lower in comparison with the controls. These data indicate that these amino derivatives have higher affinity for the 2fbt protein surface, which may translate as changes in the biological activity of the WRN exonuclease and induce changes in cancer cell growth