Maiti Motilal, Kumar Gopinatha Suresh
Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, Kolkata 700 032, India.
Med Res Rev. 2007 Sep;27(5):649-95. doi: 10.1002/med.20087.
Alkaloids occupy an important position in chemistry and pharmacology. Among the various alkaloids, berberine and coralyne of the protoberberine group, sanguinarine of the benzophenanthridine group, and aristololactam-beta-d-glucoside of the aristolochia group have potential to form molecular complexes with nucleic acid structures and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights (i) the physicochemical properties of these alkaloids under various environmental conditions, (ii) the structure and functional aspects of various forms of deoxyribonucleic acid (DNA) (B-form, Z-form, H(L)-form, protonated form, and triple helical form) and ribonucleic acid (RNA) (A-form, protonated form, and triple helical form), and (iii) the interaction of these alkaloids with various polymorphic DNA and RNA structures reported by several research groups employing various analytical techniques like absorbance, fluorescence, circular dichroism, and NMR spectroscopy; electrospray ionization mass spectrometry, thermal melting, viscosity, and DNase footprinting as well as molecular modeling and thermodynamic studies to provide detailed binding mechanism at the molecular level for structure-activity relationship. Nucleic acids binding properties of these alkaloids are interpreted in relation to their biological activity.
生物碱在化学和药理学中占据重要地位。在各种生物碱中，原小檗碱类的小檗碱和珊瑚碱、苯并菲啶类的血根碱以及马兜铃类的马兜铃内酰胺-β-D-葡萄糖苷有与核酸结构形成分子复合物的潜力，并因其潜在的临床和药理效用而受到近期关注。本综述重点介绍了：（i）这些生物碱在各种环境条件下的物理化学性质；（ii）各种形式的脱氧核糖核酸（DNA）（B型、Z型、H（L）型、质子化形式和三螺旋形式）和核糖核酸（RNA）（A型、质子化形式和三螺旋形式）的结构和功能方面；以及（iii）几个研究小组采用吸光度、荧光、圆二色性和核磁共振光谱等各种分析技术报道的这些生物碱与各种多态性DNA和RNA结构的相互作用；电喷雾电离质谱、热熔解、粘度和DNA酶足迹分析以及分子建模和热力学研究，以在分子水平上提供详细的结合机制，用于结构-活性关系。这些生物碱的核酸结合特性与其生物活性相关联进行解释。
