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Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products

机译：CC-1065和杜卡霉素天然产物家族的化学和生物探索

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CC-1065, the duocarmycins and yatakemycin are members of a family of ultrapotent antitumour antibiotics that have been the subject of extensive investigations due to their mode of action and potential in the design of new anticancer therapeutics. The natural products and their analogues exert their effects through a sequence selective alkylation of duplex DNA in the minor groove at the N3 of adenine. An understanding of their structure and its effect on biological activity has been derived through chemical synthesis and has also generated new potential lead compounds. These studies form the first section of the review. The desire to progress these compounds to clinic has also led to studies of bioconjugation and prodrug formation and this is discussed in the second section of the review. The combination of synthesis with key biological experiments is a powerful tool to define the requirements for the development of natural products as potential therapeutic agents. The studies described herein form an excellent paradigm for the study and development of other natural products.
机译：CC-1065，duocarcincins和yatakemycin是超有效抗肿瘤抗生素家族的成员，由于其作用方式和设计新抗癌治疗剂的潜力，它们已成为广泛研究的对象。天然产物及其类似物通过腺嘌呤N3处小沟中双链DNA的序列选择性烷基化发挥作用。通过化学合成已经了解了它们的结构及其对生物活性的影响，并且还产生了新的潜在先导化合物。这些研究构成了评论的第一部分。将这些化合物推向临床的愿望也导致了对生物结合和前药形成的研究，这在本综述的第二部分中进行了讨论。合成与关键生物学实验的结合是确定天然产物作为潜在治疗剂开发要求的有力工具。本文所述的研究形成了研究和开发其他天然产物的极佳范例。

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