Inclusion complex of a new propiconazole derivative with beta-cyclodextrin: NMR, ESI-MS and preliminary pharmacological studies.
Inclusion complex of a new propiconazole derivative with beta-cyclodextrin: NMR, ESI-MS and preliminary pharmacological studies.
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DOI：
10.1016/j.rinphs.2011.07.001
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发表时间：
2011-05-01
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影响因子：
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通讯作者：
Simionescu, Bogdan C
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文献类型：
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作者：
Marangoci, Narcisa;Mares, Mihai;Simionescu, Bogdan C
以硝酸丙环唑（Propiconazole，PCZ）为原料，经酸性硝化剂硝化，制备了硝酸丙环唑（Propiconazole，NO3 PCZ）-β-环糊精（beta-CD）包合物。用NMR、ESI-MS、TGA、DSC等方法研究了NO_3PCZ与β-CD形成包合物的过程。利用HMBC相关谱中的未去耦信号，测定了PCZ和NO_3PCZ化合物三唑环上CH的偶合常数（PCZ为（1）J（HC）_3 = 207 Hz，（1）J（CH）_5 = 214 Hz; NO_3PCZ为（1）J（HC）_3 = 208 Hz，（1）J（CH）_5 = 215 Hz），证实了两种形式的杂环骨架几何结构相同。通过ESI-MS确定络合物的1：1化学计量，并使用DMSO中的Scott方程和水中的Higuchi和Connors方程进行确认。绘制了NO3 PCZ在β-CD存在下在蒸馏水中的溶解度曲线，得到了AL型溶解度图。通过DLS研究测定了NO3 PCZ在水中的溶解度。结果表明，NO3 PCZ包封在β-CD空腔内，在DMSO中的结合常数为330 M-1，在水中的结合常数为975 M-1。初步药理研究表明，NO3 PCZ及其包合物的抗真菌活性高于其类似物。该包合物的急性毒性小于纯药物或修饰药物，推荐包合物作为未来有前途的治疗剂。
A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with beta-cyclodextrin (beta-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with beta-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=207Hz, (1)J(CH)5=214Hz, for PCZ; (1)J(HC)3=208Hz and (1)J(CH)5=215Hz, 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 beta-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 beta-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.