Therapeutic Potential ofNucleicAcid-Binding IsoquinolineAlkaloids: BindingAspects and Implications for Drug Design
2011
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.
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