Pezzuto J M
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
Biochem Pharmacol. 1997 Jan 24;53(2):121-33. doi: 10.1016/s0006-2952(96)00654-5.
Natural product drugs play a dominant role in pharmaceutical care. This is especially obvious in the case of antitumor drugs, as exemplified by paclitaxel (Taxol), vincristine (Oncovin), vinorelbine (Navelbine), teniposide (Vumon), and various water-soluble analogs of camptothecin (e.g., Hycamtin). The most efficient method of discovering drugs such as these (i.e. novel chemical prototypes that may function through unique mechanisms of action) is bioactivity-guided fractionation, and it is certain that additional natural product drugs, some of which should be useful for the treatment of humans, remain to be discovered. For the commercial procurement of structurally complex natural product drugs, isolation from plant material may be most practical. With the advent of combinatorial chemistry and high throughput screening, however, even greater progress may now be expected with natural product leads. While systemic drug therapy, to an appreciable extent based on natural products, has been the mainstay of pharmaceutical care, the logic of disease prevention is overwhelming. Bearing in mind the pandemic nature of cancer, a proposal is put forth to create a cancer chemoprevention drug formulation for utilization on a widespread basis by the general population. Cancer chemopreventive agents, many of which are natural products, are capable of preventing or inhibiting the process of carcinogenesis. As with other pharmaceutical agents useful for disease prevention, a pharmacoeconomic analysis of a cancer chemopreventive formulation would need to be considered, and the composition of the formulation should improve over time. Nonetheless, implementation should commence immediately.
天然产物药物在药物治疗中起着主导作用。这在抗肿瘤药物方面尤为明显,例如紫杉醇(泰素)、长春新碱(安可平)、长春瑞滨(诺维本)、替尼泊苷(威猛)以及喜树碱的各种水溶性类似物(如拓扑替康)。发现这类药物(即可能通过独特作用机制发挥作用的新型化学原型)的最有效方法是生物活性导向分级分离,而且肯定还有其他天然产物药物有待发现,其中一些对人类治疗应该是有用的。对于结构复杂的天然产物药物的商业采购,从植物材料中分离可能是最实际的方法。然而,随着组合化学和高通量筛选的出现,现在有望在天然产物先导物方面取得更大进展。虽然很大程度上基于天然产物的全身药物治疗一直是药物治疗的主要支柱,但疾病预防的逻辑性更为突出。考虑到癌症的流行性质,提出一项建议,即开发一种癌症化学预防药物制剂,供普通人群广泛使用。许多癌症化学预防剂是天然产物,能够预防或抑制致癌过程。与其他用于疾病预防的药物一样,需要考虑对癌症化学预防制剂进行药物经济学分析,并且制剂的成分应随着时间的推移而改进。尽管如此,应立即开始实施。