title: Theoretical and experimental study of inclusion complexes formed by isoniazid and modified β-cyclodextrins: 1H NMR structural determination and antibacterial activity evaluation.
abstract: Me-β-cyclodextrin (Me-βCD) and HP-β-cyclodextrin (HP-βCD) inclusion complexes with isoniazid (INH) were prepared with the aim of modulating the physicochemical and biopharmaceutical properties of the guest molecule, a well-known antibuberculosis drug. The architectures of the complexes were initially proposed according to NMR data Job plot and ROESY followed by density functional theory (DFT) calculations of (1)H NMR spectra using the PBE1PBE functional and 6-31G(d,p) basis set, including the water solvent effect with the polarizable continuum model (PCM), for various inclusion modes, providing support for the experimental proposal. An analysis of the (1)H NMR chemical shift values for the isoniazid (H6',8' and H5',9') and cyclodextrins (H3,5) C(1)H hydrogens, which are known to be very adequately described by the DFT methodology, revealed them to be extremely useful, promptly confirming the inclusion complex formation. An included mode which describes Me-βCD partially enclosing the hydrazide group of the INH is predicted as the most favorable supramolecular structure that can be used to explain the physicochemical properties of the encapsulated drug. Antibacterial activity was also evaluated, and the results indicated the inclusion complexes are a potential strategy for tuberculosis treatment.
authors: Grupo de Química Supramolecular e Biomimética (GQSB), Departamento de Química, Universidade Federal de Viçosa (UFV) , 36570-000, Viçosa, Minas Gerais, Brazil.
authors: Milena G
authors: MG
authors: Teixeira
authors: João V
authors: JV
authors: de Assis
authors: Cássia G P
authors: CG
authors: Soares
authors: Mateus F
authors: MF
authors: Venâncio
authors: Juliana F
authors: JF
authors: Lopes
authors: Clebio S
authors: CS
authors: Nascimento
authors: Cleber P A
authors: CP
authors: Anconi
authors: Guilherme S L
authors: GS
authors: Carvalho
authors: Cristina S
authors: CS
authors: Lourenço
authors: Mauro V
authors: MV
authors: de Almeida
authors: Sergio A
authors: SA
authors: Fernandes
authors: Wagner B
authors: WB
authors: de Almeida
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D004305:Dose-Response Relationship, Drug; D002479:Inclusion Bodies / Q000737:chemistry*; D007538:Isoniazid / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011522:Protons; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011522:Protons; D047392:beta-Cyclodextrins; D007538:Isoniazid