Dataset Information

Anti-Tumor Efficiency of Perillylalcohol/?-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

ABSTRACT: The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with ?-cyclodextrin (?-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and ?-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the ?-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the ?-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/?-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/?-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

SUBMITTER: Rezende AA

PROVIDER: S-EPMC7916601 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

Rezende Allan A AA Santos Rafael S RS Andrade Luciana N LN Amaral Ricardo G RG Pereira Matheus M MM Bani Cristiane C Chen Mo M Priefer Ronny R da Silva Classius F CF de Albuquerque Júnior Ricardo L C RLC Souto Eliana B EB Severino Patrícia P

Pharmaceutics 20210210 2

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD ca ...[more]

PMID: 33578857

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Project description:BackgroundIn this study we investigated the predictability of three thermodynamic quantities related to complex formation. As a model system we chose the host-guest complexes of beta-cyclodextrin (beta-CD) with different guest molecules. A training dataset comprised of 176 beta-CD guest molecules with experimentally determined thermodynamic quantities was taken from the literature. We compared the performance of three different statistical regression methods - principal component regression (PCR), partial least squares regression (PLSR), and support vector machine regression combined with forward feature selection (SVMR/FSS) - with respect to their ability to generate predictive quantitative structure property relationship (QSPR) models for DeltaG degrees, DeltaH degrees and DeltaS degrees on the basis of computed molecular descriptors.ResultsWe found that SVMR/FFS marginally outperforms PLSR and PCR in the prediction of DeltaG degrees, with PLSR performing slightly better than PCR. PLSR and PCR proved to be more stable in a nested cross-validation protocol. Whereas DeltaG degrees can be predicted in good agreement with experimental values, none of the methods led to comparably good predictive models for DeltaH degrees. In using the methods outlined in this study, we found that DeltaS degrees appears almost unpredictable. In order to understand the differences in the ease of predicting the quantities, we performed a detailed analysis. As a result we can show that free energies are less sensitive (than enthalpy or entropy) to the small structural variations of guest molecules. This property, as well as the lower sensitivity of DeltaG degrees to experimental conditions, are possible explanations for its greater predictability.ConclusionThis study shows that the ease of predicting DeltaG degrees cannot be explained by the predictability of either DeltaH degrees or DeltaS degrees. Our analysis suggests that the poor predictability of TDeltaS degrees and, to a lesser extent, DeltaH degrees has to do with a stronger dependence of these quantities on the structural details of the complex and only to a lesser extent on experimental error.

Project description:Styryllactones, a class of compounds obtained from the genus Goniothalamus (Annonaceae), have demonstrated in vitro antitumor activity. However, the aqueous solubility of these compounds is poor. In this study, we identified the absolute configurations of the previously isolated compounds, which were first isolated in our laboratory, by single-crystal X-ray diffraction analysis using Cu Kα radiation. Subsequently, the antitumor activities of the compounds were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining in four tumor cell lines. The induced apoptosis activity of leiocarpin E-7'-Monoacetate was studied by an annexin V fluorescein isothiocyanate/propidium iodide double-staining experiment, and the caspase activity was tested in the SW1116 cell line. The results demonstrated that the antitumor activities of cheliensisin A and goniodiol-7-monoacetate were limited by their poor water solubility. To address this issue, hydroxypropyl-β-cyclodextrin (HP-β-CD) complexes of the compounds were synthesized by the saturated aqueous method. The complexes were then analyzed using a differential scanning calorimeter. The IC50 of cheliensisin A was reduced by 45% and 58% against SW1116 and SMMC-7721 cell lines, respectively. Similarly, the IC50 of goniodiol-7-monoacetate was reduced by 55% and 34% against the two tumor cell lines, respectively. To further evaluate whether the styryllactones and complexes possessed selectivity against cancer cell lines and normal cell lines, toxicity against human normal cell line (HEK293T) was evaluated. The results demonstrated that the HP-β-CD complexes displayed more cytotoxicity than the respective pristine compounds against the HEK293T cell line. However, there existed a therapeutic window when the complexes were applied against cancer cell lines. In summary, the synthesis of several styryllactone compounds complexed with HP-β-CD was reported for the first time. These complexes could significantly enhance the cytotoxic effects of styryllactone compounds.

Dataset Information

Anti-Tumor Efficiency of Perillylalcohol/?-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

Publications

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model.

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