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

Narcisa Marangoci; Mihai Mares; Mihaela Silion; Adrian Fifere; Cristian Varganici; Alina Nicolescu; Calin Deleanu; Adina Coroaba; Mariana Pinteala; Bogdan C Simionescu

doi:10.1016/j.rinphs.2011.07.001

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

Results Pharma Sci. 2011 Aug 1;1(1):27-37. doi: 10.1016/j.rinphs.2011.07.001. eCollection 2011 May.

Affiliations

¹ Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, 41A Aleea Grigore Ghica-Voda, 700487 Iasi, Romania.
² Laboratory of Antimicrobial Chemotherapy, Department of Public Health, "Ion Ionescu de la Brad" University, 8 Aleea Sadoveanu, 700489 Iasi, Romania.
³ Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, 41A Aleea Grigore Ghica-Voda, 700487 Iasi, Romania ; Department of Natural and Synthetic Polymers, "Gh. Asachi" Technical University of Iasi, 73 B-dul Dimitrie Mangeron, 700050 Iasi, Romania.
⁴ Centre of Advanced Research in Bionanoconjugates and Biopolymers, "Petru Poni" Institute of Macromolecular Chemistry, 41A Aleea Grigore Ghica-Voda, 700487 Iasi, Romania ; Institute of Organic Chemistry, Spl. Independentei 202-B, RO-060023 Bucharest, Romania.

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.

Keywords: Antifungal activity; Inclusion complex; Propiconazole; β-Cyclodextrin.