Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular modeling.
In this work we prepared and characterized an inclusion complex of the dihydropteroate synthase inhibitor sulfadiazine (SDZ) in 2-hydroxypropyl-beta-cyclodextrin (HPBCD). From the phase-solubility diagram we observed an increase in the water solubility of the drug, calculating a binding constant of 1879M(-1). The inclusion mode involves a NH(2)-in orientation of the drug in the HPBCD cavity, according to the 2D NMR (ROESY) data and confirmed by molecular modeling using the semiempirical PM6 and RM1 methods.
de Araújo
Márcia Valéria Gaspar
MV
Departamento de Química, Universidade Federal de Sergipe (UFS), Av. Marechal Rondon s/n, Campus Universitário Prof. José Aloísio de Campos, CEP 491000-000, São Cristóvão, SE, Brazil.
Vieira
Elze Kelly Barbosa
EK
Silva Lázaro
Gilderman
G
Conegero
Leila Souza
LS
Almeida
Luís Eduardo
LE
Barreto
Ledjane Silva
LS
da Costa
Nivan Bezerra
NB
Gimenez
Iara F
IF
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors; D004337:Drug Carriers / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D044367:Phase Transition; D012995:Solubility; D013329:Structure-Activity Relationship; D013411:Sulfadiazine / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D004791:Enzyme Inhibitors; D047392:beta-Cyclodextrins; D014867:Water; D013411:Sulfadiazine; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004094:Dihydropteroate Synthase