Damiana da Rocha Vianna

The Antioxidant Activity of Coumarins and Flavonoids

Coumarins and flavonoids are heterocyclic molecules that have been associated with beneficial effects on human health, such as reducing the risk of cancer, diabetes, cardiovascular and brain diseases. These effects are thought to be related to the radical scavenging effect, due to their antioxidant activities, along with other possible mechanisms, such as anti-inflammatory properties and interaction with several enzymes. Over the past two decades, there have been an increasing number of publications on coumarins and flavonoids, which demonstrate the importance of understanding the chemistry behind the antioxidant activities of both natural and synthesized compounds, considering the benefits from their dietary ingestion as well as pharmacological use. This work aims to review the antioxidant effects of coumarin and flavonoid molecules in humans and the structural aspects that contribute to these effects.

Evaluation of the Antioxidant Capacity of Synthesized Coumarins

Coumarins are secondary metabolites that are widely distributed within the plant kingdom, some of which have been extensively studied for their antioxidant properties. The antioxidant activity of coumarins assayed in the present study was measured by different methods, namely the 1,1-diphenyl-2-picryl-hydrazyl (DPPH•) method, cyclic voltammetry and the antioxidant capacity against peroxyl radicals (ACAP) method. The 7,8-dihydroxy-4-methylcoumarin (LaSOM 78), 5-carboxy-7,8-dihydroxy-4-methylcoumarin (LaSOM 79), and 6,7-dihydroxycoumarin (Esculetin) compounds proved to be the most active, showing the highest capacity to deplete the DPPH radicals, the highest antioxidant capacity against peroxyl radicals, and the lowest values of potential oxidation.

Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species

The coumarins 5-methoxy-6,7-methylenedioxycoumarin 1 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin 2 and 5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin 3 isolated from Pterocaulon species showed significant cytotoxicity against two glioma cells lines. Compound 1 presented IC(50) values of 34.6 μM and 31.6 μM against human (U138-MG) and rat (C6) glioma cells, respectively, and this compound was at least two times more potent than compounds 2 and 3. This result could be explained by the planar conformation adopted by 1 through a non-classical hydrogen bond between a hydrogen of the methoxy and the oxygen of the methylenedioxy groups. Another important finding was that the cytotoxic effect induced by 1 in glioma cells was not observed in organotypic cultures, indicating a selective cytotoxicity for tumor cells.

4-Methylcoumarins with cytotoxic activity against T24 and RT4 human bladder cancer cell lines

Bladder cancer is one of the most prevalent malignancies of the genitourinary tract, and approximately 25% of patients develop superficial cancers with invasive and metastatic pathology. Coumarins and their derivatives have antiproliferative activity and induce apoptosis in several cancer cell lines. Due to the potential therapeutic applications of these compounds, a series of 4-methylcoumarins were synthesized to investigate the antitumor cytotoxic effect in the T24 and RT4 human bladder cancer cell lines. The microwave-assisted synthesis of the coumarinsvia Pechmann condensation with modifications at position 7 was performed with excellent yields (74–100%). The 7,8-dihydroxy-4-methyl-2-oxo-2H-chromene-5-carboxylic acid derivative (3c) exhibited greater cytotoxicity against T24 cells, which represent a more malignant cell line compared to RT4. In the T24 cells, cell cycle analysis revealed a large number of cells in the sub-G1 phase after treatment with 3c, which is indicative of apoptosis. Apoptotic death was confirmed by annexin V staining assay. Based on the chemical structures of the compounds, it is suggested that the 5-carboxycoumarin ring group has a positive influence on the cytotoxic activity. These results indicate that these new compounds are promising for further chemical modulation to discover a new antitumor agent.

Electroporation and iontophoretic for drug delivery across the skin

The development of dermal therapeutic systems, primarily aimed at overcoming skin property problems, has increased in recent years, with the stratum corneum representing the main barrier against drug permeation. The interaction of chemical or physical promoters (such as electroporation and iontophoresis) with the skin can increase the influx of drugs. Mechanical, chemical, and electrical techniques have been reported to improve cutaneous permeation. As such, electroporation and iontophoresis represent commonly used techniques. Electroporation is a transitory structural perturbation of the lipid bilayer membranes through the application of high voltage pulses. Its application can be used alone or in combination with iontophoresis to expand the range of drug permeation. The influence of electrical parameters (frequency of pulse, electric field power, etc.) on the physicochemical properties of the drug and of the formulation on the efficacy transport has been well-described in prior literature. However, studies are still warranted in an attempt to assure effectiveness and security when using these techniques.