Molecular Dynamics Study of Sorafenib Anti-Cancer Drug: Inclusion Complex in Amphiphilic Cyclodextrin

Cyclodextrins (CDs) are cyclic oligosaccharides able to solubilize hydrophobic drugs in water enhancing their bioavailability. Sorafenib (SOR) is a lipophilic oral multikinase inhibitor that impedes proliferation, angiogenesis, and invasion of cancer cells with low water-solubility. Recently, amphiphilic cyclodextrins (aCDs) have been investigated as possible nanocarrier for systemic administration of SOR increasing its bio-availability. A theoretical study about inclusion complexes of SOR drug and a model of aCD system using molecular mechanics (MM) and molecular dynamics (MD) methods is here reported. At first, the single molecule aCD (SC6OH, heptakis(2-O-oligo(ethylene oxide)-6-hexylthio)-𝜷-CD bearing 14 units of ethylene-oxide at the CD secondary rim) and SOR drug are studied. Then, the interaction between aCD and SOR is investigated. The theoretical results display different types of interaction geometries. The most stable geometry of the host-guest complex showed the lowest potential and favorable interaction energy and the fluorine atoms of SOR drug molecule are directed toward the hydrophobic primary rim of the aCD, while the part of the SOR rich in oxygen atoms is directed toward the hydrophilic secondary rim. This theoretical result is in a good agreement with NMR data in literature about same aCD as host of Sorafenib anti-cancer drug.