Eugenol β-Amino/β-Alkoxy Alcohols with Selective Anticancer Activity

Abstract

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.

Inula viscosa (L.) Aiton Ethanolic Extract Inhibits the Growth of Human AGS and A549 Cancer Cell Lines

“…I. viscosa ethanolic extract was solubilized in DMSO, in stocks of 50 mg/mL. For the assessment of viability, a resazurin‐based method was used [70] . AGS and HaCaT cells were plated at a density of 1.5×10 4 cells/well, while A549 cell lines was seeded at a density of 1.0×10 4 cells/well.…”

Structural modification of naturally-occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells

“…Chemical derivatization has been proven to enhance their cytotoxic activities. A study conducted with β-amino and β-alkoxy alcohols derivatives of eugenol showed these molecules possessed an enhanced but also selective anticancer activity [9]. Similar claims have been made for derivatives of thymol and flavanones [10,11].…”

“…Cells were cultured at the same density described for the MTT assay, in the presence of the molecules under study. After incubation, the culture medium was replaced by 50 μL of ultra-pure water, plates being incubated for 30 min at 37ºC and immediately frozen at -80 • C. DNA quantification was performed in a triplicate pool using a QubitTM 1X dsDNA HS Assay Kit according to manufacturer's instructions [19].…”

Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog

“…The cells were seeded in 96-well plates; human non-small cell lung cancer cells (A549) at a density of 10,000 cells/well at 24 h, 5000 cells/well at 48 h, and 2500 cells/well at 72 h; human gastric cancer cells (AGS) were seeded at a density of 15,000 cells/well at 24 h, 10,000 cells/well at 48 h, and 5000 cells/well at 72 h; and HaCaT cells were seeded at 15,000 cells/well at 24 h and allowed to attach for 24 h under the conditions described above, as reported before [ 28 ]. After an incubation period of 24, 48, or 72 h with the compounds, a 0.5 mg/mL MTT solution was added and incubated for 2 h. The formazan in each well was dissolved in a solution of 3:1 DMSO/isopropanol.…”

“…AGS cells were plated at the same density mentioned above for the MTT assay and exposed to Br-Clm for 24 h, as previously determined [ 28 ]. Caspase-3, -8, and -9 activity was assessed using an Abcam’s Caspase Multiplex Activity Assay Kit (Fluorometric).…”