A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl-7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c and 10d, exhibited the highest activity (IC50-SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity.

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 3e and 3i (for SW480) and 3a, 3e and 3k (for SW620) displayed the best cytotoxic activity with IC50 values ranging from 11.52 ± 2.78 to 29.33 ± 4.73 µM for both cell lines, with selectivity indices (SI) higher than 1, after 48 h of treatment. Selectivity indices were even higher than those reported for the reference drug, 5-fluorouracil (SI = 0.96), the starting compound resveratrol (SI = 0.45) and the equimolar mixture of curcumin plus resveratrol (SI = 0.77). The previous hybrids showed good antiproliferative activity.

To study cross-resistance to Photofrin (PF) photosensitization, a Friend leukaemia cell line (ADM-RFLC) with a high level of multi-drug resistance (MDR) and the parental sensitive cell line (FLC) have been used. PF uptake measured by HPLC shows a similar intracellular drug accumulation in both cell lines. The ID50s for cell growth inhibition by PF are also similar after exposure in the dark in the two cell lines, while after illumination they are slightly lower in ADM-RFLC than in FLC cells. Moreover, verapamil, known to reverse the MDR phenotype induced by P-glycoprotein over-expression (the drug efflux mechanism), affects equally ADM-RFLC and FLC cells sensitivity to PF. In addition, photodynamic treatment with PF did not reverse the resistance to rhodamine 123 and aclarubicin, but partly reverses resistance of ADM-RFLC cells to antitubulin drugs such as vinblastine or vincristine. These latter results could have clinical application in the treatment of tumours expressing the MDR phenotype.

This study aimed to evaluate whether near‐infrared spectroscopy ( NIRS )‐derived reperfusion slope would detect the effects of a 12‐week rehabilitation program on lower limb microvascular responsiveness in patients with coronary heart disease ( CHD ). Ten CHD patients (7 males and 3 females; 57.3 ± 7.6 years) underwent 12 weeks of drug treatment and high‐intensity interval training ( HIIT ), 2 times per week (40 min/session). Microvascular responsiveness was assessed by using NIRS assessment of muscle oxygen saturation (StO 2 ) combined with a vascular occlusion test ( VOT ) ( NIRS ‐ VOT ). NIRS ‐ VOT measures were taken at pre‐ and postintervention, and microvascular responsiveness was evaluated by examining the slope 2 of re‐oxygenation rate (slope 2 StO 2 ) and the area under the curve (StO 2 AUC ) of StO 2 signal following cuff release subsequent to a 5‐min occlusion period. The slope 2 StO 2 was significantly steeper after 12 weeks of training (4.8 ± 1.6% sec −1 ) compared to the pretraining (3.1 ± 1.6% sec −1 ) ( P < 0.05). The area under the curve for the change in the % StO 2 signal during re‐oxygenation increased significantly from 3494 ± 2372%∙sec at pretraining to 9006 ± 4311%∙sec at post‐training ( P < 0.05). NIRS ‐ VOT technique detected the improvements of 12 weeks of rehabilitation program in the lower limb microvascular responsiveness of CHD patients.

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