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A mixed DFT‐MD methodology for the in silico development of drug releasing macrocycles. Calix and thia‐calix[ N ]arenes as carriers for Bosutinib and Sorafenib
Author(s) -
GalindoMurillo Rodrigo,
AguilarSuárez Luis Enrique,
BarrosoFlores Joaquín
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.24281
Subject(s) - bosutinib , chemistry , sorafenib , in silico , combinatorial chemistry , drug , stereochemistry , computational chemistry , tyrosine kinase , nilotinib , pharmacology , medicine , biochemistry , signal transduction , cancer research , hepatocellular carcinoma , gene , biology
Interaction energies between a family of 36 calix[ n ]arenes, their corresponding thia ‐ analogues, and two commercially available second generation tyrosine kinase III inhibitors—Bosutinib and Sorafenib—were calculated through DFT methods at the B97D/6‐31G( d , p ) level of theory, based on Natural Population Analysis, for the in silico development of suitable drug carriers based on the aforementioned macrocycles which can increase their bioavailability and in turn their pharmaceutical efficiency. Molecular Dynamics simulations (production runs: +500 ns) using the General Amber Force Field were also carried out in order to assess the releasing process of these drugs in an explicit aqueous environment. In total, 144 host–guest complexes are examined. According to our results, five‐membered SO 3 H and i –Pr functionalized‐calixarenes are the best candidates for Sorafenib‐carriers while six‐membered ones SO 3 H and C 2 H 4 NH 2 functionalized– are the lead candidates for Bosutinib‐carriers. © 2015 Wiley Periodicals, Inc.