Abstract
Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form) and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity.
Highlights
The mode of action of many drugs in clinical use for the treatment of cancer, genetic disorders, and viral diseases is believed to be based on their binding to nucleic acids and subsequent modification of the genetic material [1, 2]
The discovery of the double helical structure of deoxyribonucleic acid (DNA) by Watson and Crick in 1953 [3] and the subsequent revelations relating to the structural features to the basic functional properties of DNA such as replication and transcription have proven the utility of DNA as a potential target for the development of biologically active agents [4, 5]
These structure-activity relationships are consistent with a model for Topoisomerase I (Topo I) poisoning by protoberberines in which both alkaloid-DNA and alkaloid-enzyme interactions are necessary for stabilization of the ternary (Topo I-DNAalkaloid) cleavable complex (Figure 10)
Summary
The mode of action of many drugs in clinical use for the treatment of cancer, genetic disorders, and viral diseases is believed to be based on their binding to nucleic acids and subsequent modification of the genetic material [1, 2]. Intercalation occurs when planar aromatic molecules are sandwiched between two adjacent base pairs of nucleic acids. Nonintercalative binding occurs in the major or minor grooves of nucleic acids without inserting any part of the binding molecule between base pairs. The physical and molecular basis of binding of natural alkaloids to nucleic acids has been a subject of extensive study in the recent past [14,15,16,17]. The intercalating ligands constitute one of the most widely studied groups as Journal of Nucleic Acids
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
