Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI–MS and preliminary pharmacological studies

Abstract

A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI-MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds ((1)J(HC)3=207 Hz, (1)J(CH)5=214 Hz, for PCZ; (1)J(HC)3=208 Hz and (1)J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI-MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents.

TGA/DTA–FTIR–MS coupling as analytical tool for confirming inclusion complexes occurrence in supramolecular host–guest architectures

“…Complexation is indicated by an increase in the thermal stability of the complexed guest as compared to that of the uncomplexed components. Also, the melting profile of the guest molecule in the inclusion complex gradually lowers in its intensity [19]. Fig.…”

“…inclusion in the ␤CD cavity the thermal stability of Bpy molecule increases, from 190 • C to 215 • C [19]. This aspect is further reflected by a significant increase in residual mass of Bpy-␤CD (19%) compared to that of pure Bpy (4.33%).…”

Etiologic Agents and Antifungal Susceptibility of Oral Candidosis from Romanian patients with HIV-infection or type 1 diabetes mellitus

“…In vitro susceptibility testing was performed following the EUCAST E. Def 7.1 guidelines (Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), 2008), for six antifungal agents: fluconazole (Sigma -St. Louis, USA), voriconazole (Pfizer Ltd. -Sandwich, UK), caspofungin (Merck & Co, Inc.), micafungin (Astellas Pharma, Japan), anidulafungin (Pfizer, Inc.) and the MXP-4509 experimental compound ("Petru Poni" Institute of Macromolecular Chemistry -Iasi, Romania), which is a triazole based nanoconjugate with β-cyclodextrin as a carrier molecule (Marangoci et al, 2011). Two reference strains (C. albicans ATCC 90028 and Candida krusei ATCC 6258) were used for quality control.…”

Topical Nanointerventions for Therapeutic and Cosmeceutical Applications

“…because of their epidermal accumulation potential, increased solubility of drug at the therapeutic site and reduced systemic side effects [ 42 , 58 ]. As an evidence, it should be noted that in an antifungal assay against 56 Candida albicans strains, such developed propiconazole nitrate, β-cyclodextrin complexes, showed remarkably low MIC 90 value of 0.0312 mg/L as compared to 128 mg/L in case of propiconazole alone [ 42 ]. As an advancement to this approach, with an anticipated additional epidermal depot effect, Hbaieb et al developed a nystatin β-cyclodextrin complex and immobilised it on silica nanoparticles which are reported to accumulate in the pilosebaceous unit of skin [ 58 ].…”