title: 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.
abstract: 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 -SO3H and i-Pr functionalized-calixarenes are the best candidates for Sorafenib-carriers while six-membered ones -SO3H and C2H4NH2 functionalized- are the lead candidates for Bosutinib-carriers.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah, 84112.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Centro Conjunto De Investigación En Química Sustentable UAEM-UNAM, Toluca, Estado De México, 50200, Mexico.
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Aguilar-Suárez
authors.affiliation: Centro Conjunto De Investigación En Química Sustentable UAEM-UNAM, Toluca, Estado De México, 50200, Mexico.
authors.forename: Joaquín
authors.identifier: http://orcid.org/0000-0003-0554-7569
authors.initials: J
authors.lastname: Barroso-Flores
mesh_terms: D000814:Aniline Compounds; D047250:Calixarenes / Q000737:chemistry*; D003198:Computer Simulation; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives*; D009570:Nitriles; D010671:Phenylurea Compounds; D011789:Quantum Theory; D011804:Quinolines; D000077157:Sorafenib
chemical_list: D000814:Aniline Compounds; D004337:Drug Carriers; D009570:Nitriles; D010671:Phenylurea Compounds; D011804:Quinolines; D047250:Calixarenes; D009536:Niacinamide; C471992:bosutinib; D000077157:Sorafenib
keywords: DFT; NBO; calixarenes; drug carriers; molecular dynamics