Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian carcinoma cells). Some compounds showed IC50 values < 0.3 μM. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC), V79 and L929 cells. Mechanistic role for NAD(P)H:Quinone Oxidoreductase 1 (NQO1) was also elucidated. These compounds could provide promising new lead derivatives for more potent anticancer drug development and delivery, and represent one of the most active classes of lapachones reported.
Two new benzothiadiazole-triazole-linked lapachone derivatives were designed, synthesized and characterized by 1D and 2D NMR spectroscopy. Their photophysical properties were also investigated.Theoretical calculations (DFT), based on the molecular design of the new compounds, allowed a better understanding of the derivatives' stability and behaviour, especially in the excited state. This manuscript also describes a discussion on the molecular architecture which is based on two substitutions at positions 4-and 7-of the important 2,1,3-benzothiadiazole (BTD) core. One side is replaced by a group capable of performing an ESIPT (excited-state intramolecular proton transfer) stabilizing process, and the other side is substituted by a triazole-containing group. This triazole ring acts as the linker between the BTD core and a group of known antitumoral activity i.e. a nor-b-lapachone derivative. These novel fluorescent compounds had their biological activities evaluated against twenty cancer cell lines and three normal cells with promising results. Finally, due to their interesting photophysical properties and good fluorescence, bioimaging experiments were conducted, and these dyes were tested as fluorescent cell-imaging probes, thus showing their preferable cellular location in MDA-MB-231 cancer cells (a breast-invasive cancer-cell lineage).
1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 μM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.
Abstract:In continuation of our quest for new redox-modulating catalytic antitumor molecules, selenium-containing quinone-based 1,2,3-triazoles were synthesized using rhodium-catalyzed C-H bond activation and click reactions. All compounds were evaluated against five types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), SF295 (human glioblastoma cells), NCIH-460 (human lung cells) and PC3 (human prostate cancer cells). Some compounds showed good activity with IC 50 values below 1 µM. The cytotoxic potential of the naphthoquinoidal derivatives was also evaluated in non-tumor cells, exemplified by L929 cells. Overall, these compounds represent promising new lead derivatives and stand for a new class of chalcogenium-containing derivatives with potential antitumor activity.
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