Antitumor activities of a newly synthesized shikonin derivative, 2-hyim-DMNQ-S-33

2- or 6-(1-hydroxyiminoalkyl)-5,8-dimethoxy-1, 4-naphthoquinone(2- or 6-hyi m-DMNQ) derived from the roots of Lithospermum erythrorhizon was synthesize d for the evaluation of antitumor activities. Among those derivatives, 2-hy im-DMNQ-S33 was found to be a potent anticancer agent. This compound suppre ssed the proliferation of Radiation Induced Fibrosarcoma (RIF) cells in a d ose-dependent manner. 2-hyim-DMNQ-S33 significantly prolonged the survival time by 239% as compared with Sarcoma 180 tumor-bearing control mice in viv o. We found that the compound significantly suppressed phosphorylation of e xtracellular signal-regulated kinase (pERK) and activated c-jun-N-terminal kinase (JNK) and protein kinase C (PKC)-alpha following 4 h-treatment. Thes e findings indicate that 2-hyiin-DMSQ-S33 exerts antitumor activities by re gulating pERK, JNK and PKC-alpha. (C) 2001 Elsevier Science Ireland Ltd. Al l rights reserved.