Therapeutic Potential of Nucleic Acid-Binding Isoquinoline Alkaloids: Binding Aspects and Implications for Drug Design

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. (C) 2010 Wiley Periodicals, Inc. Med Res Rev, 31, No. 6, 821-862, 2011