Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells.

Coumarins possess a wide array of therapeutic capabilities, but often with unclear mechanism of action. We tested a small library of 18 coumarin derivatives against human invasive breast ductal carcinoma cells with the capacity of each compound to inhibit cell proliferation scored, and the most potent coumarin analogues selected for further studies. Interestingly, the presence of two prenyloxy groups (5,7-diprenyloxy-4-methyl-coumarin, 4g) or the presence of octyloxy substituent (coumarin 4d) was found to increase the potency of compounds in breast cancer cells, but not against healthy human fibroblasts. The activity of potent compounds on breast cancer cells cultured more similarly to the conditions of the tumour microenvironment was also investigated, and increased toxicity was observed. Results suggest that tested coumarin derivatives could potentially reduce the growth of tumour mass. Moreover, their use as (combination) therapy in cancer treatment might have the potential of causing limited side effects.

Preparation and characterization of solid lipid nanoparticles incorporating bioactive coumarin analogues as photosensitizing agents.

Daphnetin (7,8-dihydroxy-coumarin, DAPH) is a naturally occurring coumarin presenting a wide array of biological activities. In the present study, daphnetin and its novel synthetic analogue 7,8-dihydroxy-4-methyl-3-(4-hydroxyphenyl)-coumarin (DHC) were encapsulated in solid lipid nanoparticles (SLNs) with Encapsulation Efficiency values of 80% and 40%, respectively. Nanoparticles of an average hydrodynamic diameter of approximately 250 nm were formed, showing a good stability in aqueous dispersion (polydispersity index 0.3-0.4), as determined by Dynamic Light Scattering (DLS). The SLNs were also characterized using Fourier Transform-Infrared (FT-IR) spectroscopy and Thermogravimetric Analysis (TGA). TEM images of the blank-SLNs indicated a spherical morphology and a size of 20-50 nm. The release studies of the coumarin analogues indicated a non-Fickian diffusion mechanism, while the release profiles better fitted on the Higuchi kinetic model. Moreover, the coumarin analogues and their SLNs were examined for their antioxidant activity using DPPH and anti-lipid peroxidation assays, exhibiting stronger antioxidant activity when encapsulated than in their free form. The coumarin derivatives and their SLNs were examined for their photodynamic therapy (PDT) efficacy against the human squamous carcinoma A431 cell line, with DHC coumarin both in its free and encapsulated form exhibiting significant PDT activity, reducing the cell viability to 11% after irradiation with a fluence rate of 2.16 J/cm2. Finally, the intracellular localization studies indicated the enhanced cellular uptake of the coumarin analogues when loaded in the SLNs.

Ιnclusion Complexes of Magnesium Phthalocyanine with Cyclodextrins as Potential Photosensitizing Agents.

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (ß-CD, γ-CD, HP-ß-CD, Me-ß-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release ("burst effect") of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer-Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm2), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form.