Estudo teórico das interações não covalentes dos SI-PPCs com o fondaparinux

Abstract

Cancer, one of the evils plaguing society worldwide, consists of uncontrolled cell growth and has long been considered a global public health issue. Substitution-inert polynuclear Platinum (II) compounds (SI-PPCs) have been gaining notoriety over the years for demonstrating antitumor and antimetastatic effects, as their interactions are faster and more effective compared to mononuclear compounds, such as cisplatin. Thus, several studies have been carried out in order to describe how the interaction of SI-PPCs with targets such as DNA and heparan sulfate (HS) occurs. This study aims to provide a theoretical study of the structures of three SI-PPCs, monoplatin, diplatin and triplatin, interacting with a heparan sulfate mimetic model, known as Fondaparinux (FPX). Such compounds, have the ability to interact with FPX through non-covalent bonds known as sulfate clamps and forks. The present study aims to study the formation of these clamps and forks, through theoretical calculations using the 3c method which contains three empirical corrections in its calculation protocol, in addition to showing how the London D3-BJ dispersion correction is of paramount importance for the accuracy of these calculations. The BSSE base correction showed for two systems that here were called s-MonoPt@A-FPX and s-MonoPt@AB-FPX a difference of 10 and 15 kcal.mol-1, respectively in the complexation energy in relation to the optimized molecule without BSSE. The London dispersion, D3-BJ, changes the interaction distance between atoms of the complex with FPX, i.e. these corrections are important in search of a stable structure. Another point reported was the interactions of the type clamps and sulfate forks, for monoplatin, diplatin and triplatin, showing that the method favored the formation of clamps in MonoPt and DiPt, and in TriPt there was the formation of a clamp and fork in different rings, that is, a long-range bond, and these interactions are responsible for the antitumor effect and the inhibition of angiogenesis.