Theoretical study on the interactions between ibrutinib and gold nanoparticles for being used as drug delivery in the chronic lymphocytic leukemia

A theoretical study of the interaction of ibrutinib with both cysteine!methyl-cysteine and gold surface is presented. The interest of ibrutinib is that binds through its acrylamide group with the S atom from Cys481 residue of Bruton-tyrosine-ldnase (BTK) protein and inhibits the maturation of B-lymphocytes. In a first part, the interaction of ibrutinib through its acrylamide group with cysteine/methyl-cysteine is studied in the range of 298 to 315 K to analyse the effect of increasing the temperature in the binding of the drug with the amine-acid. The interaction is favoured at physiologic temperature but its stability decreases at higher temperatures. Thus, in patients with fever the drug may present a lower effectivity and certain amount of free drug in the blood may appear increasing the risk of toxicity for them. In the second part, the interaction of ibrutinib with a gold surface was studied to explore the possibility of using gold nanoparticles as ibrutinib deliverer. The most stable interaction corresponds to the structure with the nitrogen atoms from pyrimidine moiety and from NH2 directly focused over gold atoms keeping acrylamide group of ibrutinib free for joining to BTK. Therefore, according to the theoretical results gold nanoparticles may be used as ibrutinib deliverer. (C) 2020 Elsevier B.V. All rights reserved.