Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 410 W. 12th Avenue, Columbus, OH 43210, USA.
Curr Drug Targets. 2010 Jul;11(7):812-22. doi: 10.2174/138945010791320809.
Hematologic malignancies account for a substantial percentage of cancers worldwide, and the heterogeneity and biological characteristics of leukemias and lymphomas present unique therapeutic challenges. Although treatment options exist for most of these diseases, many types remain incurable and the emergence of drug resistance is pervasive. Thus, novel treatment approaches are essential to improve outcome. Nearly half of the agents used in cancer therapy today are either natural products or derivatives of natural products. The enormous chemical diversity in nature, coupled with millennia of biological selection, has generated a vast and underexplored reservoir of unique chemical structures with biologic activity. This review will describe the investigation and application of natural products derived from higher plants in the treatment of leukemia and lymphoma and the rationale behind these efforts. In addition to the approved vinca alkaloids and the epipodophyllotoxin derivatives, a number of other plant compounds have shown promise in clinical trials and in preclinical investigations. In particular, we will focus on the discovery and biological evaluation of the plant-derived agent silvestrol, which shows potential for additional development as a new therapeutic agent for B-cell malignancies including chronic lymphocytic leukemia.
血液系统恶性肿瘤在全球癌症中占很大比例，白血病和淋巴瘤的异质性和生物学特征带来了独特的治疗挑战。尽管大多数这些疾病都有治疗选择，但许多类型仍然无法治愈，而且耐药性的出现也很普遍。因此，需要新的治疗方法来改善治疗效果。目前，癌症治疗中使用的药物近一半是天然产物或其衍生物。自然界中存在巨大的化学多样性，加上数千年的生物选择，产生了大量未被充分探索的具有生物活性的独特化学结构库。这篇综述将描述从高等植物中提取的天然产物在治疗白血病和淋巴瘤方面的研究和应用，以及这些努力的基本原理。除了已批准的长春生物碱和鬼臼毒素衍生物外，还有一些其他植物化合物在临床试验和临床前研究中显示出了希望。特别是，我们将重点介绍植物来源的药物 silvestrol 的发现和生物学评估，它显示出作为包括慢性淋巴细胞白血病在内的 B 细胞恶性肿瘤的新型治疗药物进一步开发的潜力。
