Cytotoxic Bisbenzylisoquinoline Alkaloids from <i>Stephania epigaea</i>

Abstract

Six new bisbenzylisoquinoline alkaloids (<b>1</b>–<b>6</b>) and seven known compounds (<b>8</b>–<b>14</b>) were isolated from the tubers of <i>Stephania epigaea</i>, in addition to the major alkaloid, cepharanthine (<b>7</b>). The structures of <b>1</b>–<b>6</b> were elucidated by combined spectroscopic data analysis and chemical methods, with their configurations determined from their optical rotation values and confirmed using circular dichroism. Compounds <b>1</b>–<b>6</b> belong to the oxyacanthine type of bisbenzylisoquinoline alkaloids and have a rare methylenedioxy substituent. Compound <b>1</b>, a dimer composed of benzylisoquinoline and seco-aristolactam units, represents a new type of bisbenzylisoquinoline alkaloid, while compounds <b>3</b>–<b>6</b> are bisbenzylisoquinoline <i>N</i>-oxides. These compounds were evaluated for their in vitro cytotoxicities against six human cancer cell lines (A-549, ECA109, HL-60, MCF-7, SMMC-7721, and SW480). Cepharanthine (<b>7</b>), the major component of <i>S. epigaea</i>, exhibited cytotoxicity against all of these cancer cell lines except ECA109, while its known analogue, <b>10</b>, displayed cytotoxicity against all six cancer cell lines