Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, Kolkata 700032, India.
Med Res Rev. 2011 Nov;31(6):821-62. doi: 10.1002/med.20202. Epub 2010 Jan 14.
Isoquinoline alkaloids represent a group of natural products with remarkable importance in the contemporary biomedical research and drug discovery programs. Several members of this group exhibit immense pharmacological and biological properties, including potential anticancer properties. Although the molecular targets of these alkaloids are not yet clearly delineated, extensive research in this area continues to build up new data that are clinically exploitable. The gross structural features of many of the members DNA interaction are more or less clear, but the mystery still remains on many aspects of their binding, including specificity and energetics. RNA-binding aspects of these alkaloids are being elucidated. More recent advancements in analytical instrumentation have enabled clearer elucidation and correlation of the structural and energetic aspects of the interaction. In this review, we report up-to-date details of the interaction of berberine, palmatine, and jatrorrhizine of the protoberberine group, sanguinarine from the benzophananthridine group, and several of their synthetic derivatives, such as coralyne, berberrubine, palmatrubine, and jatrorubin with nucleic acids have been reviewed. These studies, taken together up to now, have led to interesting knowledge on the mode, mechanism, specificity of binding, and correlation between structural aspects and energetics enabling a complete set of guidelines for design of new drugs. In contemporary research, several derivatives of these natural alkaloids are being prepared and investigated in several laboratories for ultimate discovery of new compounds that can be used as effective therapeutic agents.
异喹啉生物碱是一类具有重要意义的天然产物，在当代生物医学研究和药物发现计划中具有重要地位。该类化合物的许多成员表现出巨大的药理学和生物学特性，包括潜在的抗癌特性。尽管这些生物碱的分子靶点尚未明确界定，但该领域的广泛研究仍在不断积累可临床应用的数据。许多成员与 DNA 的相互作用的总体结构特征或多或少是清楚的，但它们结合的许多方面仍然存在谜团，包括特异性和能量学。这些生物碱与 RNA 的结合方面正在被阐明。分析仪器的最新进展使得对相互作用的结构和能量方面的阐明和关联更加清晰。在这篇综述中，我们报告了小檗碱、巴马汀和原小檗碱组中的药根碱、苯菲啶组中的血根碱以及几种其合成衍生物，如小檗红碱、小檗红定、巴马汀和药根碱与核酸相互作用的最新详细信息。迄今为止，这些研究导致了关于结合模式、机制、特异性以及结构和能量学之间相关性的有趣知识，为设计新药提供了一套完整的指导方针。在当代研究中，正在为几个实验室准备和研究这些天然生物碱的几种衍生物，以最终发现可作为有效治疗剂的新化合物。
