Showing papers by "John M. Pezzuto published in 2018"

Synthesis and Structure-Activity Relationships of Tetrahydro-β-carboline Derivatives as Anticancer and Cancer-chemopreventive Agents.

Abstract: Background/aim There is an unmet clinical need to develop new anticancer and chemopreventive agents. The aim of the present study was to identify β-carboline derivatives with cancer chemopreventive and therapeutic potential. Materials and methods Forty-eight tetrahydro-β-carboline derivatives were synthesized and evaluated for their anticancer and chemopreventive activities, through induction of quinone reductase 1 (QR1), aromatase inhibition, as well as inhibition of nitric oxide (NO) production. Results 2-((1-Bromonaphthalen-2-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole demonstrated the most potent activity in the QR1 induction assay with an induction ratio value of 3.2 (CD=1.3 μM). The R-isomer of the amide derivative (2-((1-bromonaphthalen-2-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-yl)(4-methylpiperazin-1-yl)methanone was the most potent inhibitor of NO production with a 50% inhibitory concentration, IC50=6.54 μM and had a low cytotoxic effect (IC50=17.98 μM) on RAW 264.7 cells. Subsequent computational docking study revealed that this compound binds to the active site of inducible nitric oxide synthase with favorable interactions. Conclusion our results provided promising β-carboline leads for further optimization and development with therapeutic potential as new chemopreventive and chemotherapy agents.

Induction of NAD (P)H: Quinone reductase 1 (QR1) and antioxidant activities in vitro of 'Toranja Burarama' (Citrus maxima [Burm.] Merr.).

Abstract: Toranja 'Burarama', Citrus maxima (Burm.) Merr. (Citrus grandis), is a new citrus discovered in the State of Espirito Santo, Brazil. As several varieties of citrus are known to possess antioxidant and cancer chemopreventive properties, the aim of the study was to evaluate in vitro if this Toranja possess these properties. The antioxidant activity, the potential to induce quinone reductase 1, and the influence on cell viability were measured. ESI(-)FT-ICR MS analysis was also performed and identified flavonoids, coumarins, and fatty acids in the extract. The ethyl acetate and methanolic extracts of the peels presented the highest antioxidant activity in vitro by DPPH (IC50 = 298.3 ± 2.6 μg/ml and 303.8 ± 0.4 μg/ml), ABTS assay (IC50 = 298.2 ± 6.4 μg/ml and 296.4 ± 2.5 μg/ml), and FRAP (IC50 = 234.6 ± 1.8 μg/ml and 398.1 ± 3.8 μg/ml). The ethyl acetate extract of the peel induced quinone reductase 1 activity in Hepa1c1c7 cells, indicating that C. maxima exhibited cancer chemopreventive properties.