Takahashi N, Kubo Y, Iwahori A, Kawai K I, Fukui T
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Biol Pharm Bull. 2000 Jun;23(6):748-54. doi: 10.1248/bpb.23.748.
Falconensones A and B are a new type of yellow pigment with structural similarity to retinoic acid isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa. In the present study we show that falconensone A alone induced apoptosis of HL60 human leukemia cells, while falconensone B, the 4'-nor-methyl derivative of falconensone A, had much lower activity. The synthetic derivatives of falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime, were more potent than natural falconensone A and B as far as the induction of apoptosis was concerned. The induction of apoptosis by the falconensones correlated with their inhibition of cell growth. In addition, falconensones A and B, and falconensone A dioxime, increased the generation of intracellular reactive oxygen species, while falconensone A p-bromophenylhydrazone was inactive. These results suggest that falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime are potential new apoptosis-inducing agents. The enhanced generation of reactive oxygen species in cells may be involved in apoptosis induced by falconensone A and falconensone A dioxime, but not by falconensone A p-bromophenylhydrazone. It is also suggested that the methyl residue at the 4' position of the falconensone A cyclopentenone ring may be essential for the induction of apoptosis. Based on these results, falconensone A and its derivatives may be clinically useful in the treatment of some leukemias.
猎鹰菌素A和B是一种新型黄色色素，其结构与视黄酸相似，从子囊菌纲真菌猎鹰埃默里盘菌或丛梗埃默里盘菌的菌丝体提取物中分离得到。在本研究中，我们发现单独的猎鹰菌素A可诱导HL60人白血病细胞凋亡，而猎鹰菌素B，即猎鹰菌素A的4'-去甲基衍生物，活性则低得多。就诱导凋亡而言，猎鹰菌素A的合成衍生物，即猎鹰菌素A对溴苯腙和猎鹰菌素A二肟，比天然的猎鹰菌素A和B更有效。猎鹰菌素诱导凋亡与其对细胞生长的抑制作用相关。此外，猎鹰菌素A和B以及猎鹰菌素A二肟可增加细胞内活性氧的产生，而猎鹰菌素A对溴苯腙则无此活性。这些结果表明，猎鹰菌素A、猎鹰菌素A对溴苯腙和猎鹰菌素A二肟是潜在的新型凋亡诱导剂。细胞内活性氧的增加可能参与了猎鹰菌素A和猎鹰菌素A二肟诱导的凋亡，但不参与猎鹰菌素A对溴苯腙诱导的凋亡。还表明，猎鹰菌素A环戊烯酮环4'位的甲基残基可能对诱导凋亡至关重要。基于这些结果，猎鹰菌素A及其衍生物在临床上可能对某些白血病的治疗有用。
