Glyoxyl analogs of indole phytoalexins: Synthesis and anticancer activity

Abstract

Glyoxyl analogs of indole phytoalexins brassinin, 1-methoxybrassinin, brassitin, 1-methoxybrassitin and 1-methoxybrassenin B were prepared, using (1H-indol-3-yl)-, (1-methoxyindol-3-yl)- and [1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl]glyoxyl chlorides as starting compounds. Synthesized products were examined for their antiproliferative activity against human cancer cell lines Jurkat (T-cell acute lymphoblastic leukemia), MCF-7 (breast adenocarcinoma, estrogen receptor-positive), MDA-MB-231 (breast adenocarcinoma, estrogen receptor-negative), HeLa (cervical adenocarcinoma), CCRF-CEM cell line (T-cell acute lymphoblastic leukemia) and A-549 cell line (lung adenocarcinoma), and their activity compared with natural phytoalexins and corresponding (1H-indol-3-yl)acetic acid derivatives. The highest potency with IC50 3.3–66.1 μmol l–1 was found for glyoxyl analogs of 1-methoxybrassenin B.

Antiproliferative Effect of Indole Phytoalexins

“…Glyoxylic analogs of natural phytoalexins, such as brassinin, brassitin, and some 1-methoxyindole phytoalexins, were synthesized. When comparing the antiproliferative activity of these derivatives to natural phytoalexins, it was shown that the most effective was an analog of glyoxylic 1-methoxybrassenin B (IC 50 3.3–66.1 μmol/L), which reduced the growth of cells in the most acute lymphoblastic leukemia line (CCRF-CEM) from a number of tested cancer cell lines (Jurkat, HeLa, MCF-7, MDA-MB231, A-549, CCRF-CEM) [87]. There are also several other studies on the anti-tumor effects of substances containing the indolyl glyoxylic group.…”

Phytoalexins from Brassicaceae: News from the front

“…chemical synthesis and/or biosynthesis and bioactivity (Pedras et al, 2003b(Pedras et al, , 2007bPedras, 2008;Kutschy and Mezencev, 2008). More specific reviews on the antiproliferative and chemopreventive activity (Mezencev et al, 2003) and detoxification (Pedras and Ahiahonu, 2005) area.…”

ROS-Dependent Antiproliferative Effect of Brassinin Derivative Homobrassinin in Human Colorectal Cancer Caco2 Cells

“…Recently, Izutani et al [6] described the ability of brassinin to inhibit cell growth in human colon cancer cells by arresting the cell cycle at the G 1 phase via increased expression of p21 and p27. In the last decade we have also documented the antiproliferative effects of brassinin or its derivatives in different cancer cells [25,26,27,28,29,30].…”