Nucleic acids binding strategies of small molecules: Lessons from alkaloids.

BACKGROUND: Nucleic acids are now important targets for therapeutic intervention. Alkaloids are an important class of molecules that have myriad therapeutic utility. Isoquinoline and benzophenanthridine alkaloids exhibit multiple pharmacological activities which are often related to their strong nucleic acid binding abilities. Therefore, a review of their interaction aspects with varying nucleic acid structures is essential for rational design and development as therapeutic agents.

SCOPE OF THE REVIEW: This work reviews the interaction of various therapeutically important isoquinoline and benzophenanthridine alkaloids with nucleic acids. The review lends insights into the molecular aspects of the interaction that is critical from the perspective of designing better therapeutics.

MAJOR CONCLUSIONS: This review provides a concise report on the recent developments and advancements on the interaction of various alkaloids with natural and synthetic nucleic acids. The review focuses on the mode, mechanism, specificity, conformational aspects and energetics of the interaction that will be helpful in the design and synthesis nucleic acid targeted alkaloid analogs.

GENERAL SIGNIFICANCE: The molecular aspects of the interaction presented here will benefit the development of effective drugs for many diseases. The fundamental results discussed in this review can serve as a database for the design and development of futuristic nucleic acid based small molecule therapeutics.