Calix[n]arene-based drug carriers: A DFT study of their electronic interactions with a chemotherapeutic agent used against leukemia
Por:
Galindo-Murillo R., Olmedo-Romero A., Cruz-Flores E., Petrar P.M., Kunsagi-Mate S., Barroso-Flores J.
Publicada:
1 may 2014
Resumen:
The suitability of eight differently substituted calix[n]arenes (with
R = -OEt; SO3H and n = 4, 5, 6, 8) as drug delivery agents for
3-phenyl-1H-[1 benzofuro[3,2-c]pyrazole (henceforth referred to as
GTP), a promising new tyrosine kinase inhibitor drug, has been analyzed
by means of DFT theoretical calculations at the B97D/6-31G(d,p) level of
theory. Geometries and interaction energies for all inclusion complexes
were calculated with NBO, as well as NBO deletion calculations in order
to evaluate the energetics of the interactions between GTP and the inner
walls of the calix[n]arene cavities. Second order perturbation theory
analysis of the charge transfer based on the NBO population analysis was
also performed to assess the energetics of the intramolecular bonding in
the host guest complexes. Bond indexes suggest the formation of
hydrogen-bonds as part of the stabilizing forces of the complex. Two
possible insertion modes were explored for the insertion of GTP in the
macrocyclic cavity yielding a total of 16 inclusion complexes studied.
Interaction energies were higher for R = SO3H. Hosts (8) and (6) (n = 8
and 6, respectively) are the most promising candidates for becoming GTP
delivery agents within the chemical space under exploration herein. (c)
2014 Elsevier B.V. All rights reserved.
Filiaciones:
Galindo-Murillo R.:
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, 2000 East 30 South Skaggs 201, Salt Lake City, UT 84112, United States
Olmedo-Romero A.:
Ctr Conjunto Invest Quim Sustentable UAEMex UNAM, Unidad San Cayetano, Toluca 50200, Estado De Mexic, Mexico
Cruz-Flores E.:
Ctr Conjunto Invest Quim Sustentable UAEMex UNAM, Unidad San Cayetano, Toluca 50200, Estado De Mexic, Mexico
Petrar P.M.:
Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University, 11, Arany Janos Str., RO-400028 Cluj-Napoca, Romania
Kunsagi-Mate S.:
Department of General and Physical Chemistry, Univ. of Pécs Ifjúság 6 Pécs H-7624, Hungary
János Szentágothai Research Center, Ifjúság 20., Pécs H-7624, Hungary
Barroso-Flores J.:
Ctr Conjunto Invest Quim Sustentable UAEMex UNAM, Unidad San Cayetano, Toluca 50200, Estado De Mexic, Mexico
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