Background: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary
biomedical research and drug discovery programs. With time, there is emerging interest in
search for better anti-cancer drugs of plant origin with high activity and lower toxicity. Most of the
chemotherapeutic agents due to their non-specific target and toxicity on active healthy cells, use is
often restricted, necessitating search for newer drugs having greater potentiality.
Objective: The review highlighted the interaction of harmalol with nucleic acids of different motifs as
sole target biomolecules and in vitro cytotoxicity of the alkaloid in human cancer cell lines with special
emphasis on its apoptotic induction ability.
Methods: Binding study and in vitro cytotoxicity was performed using several biophysical techniques
and biochemical assays, respectively.
Results: Data from competition dialysis, UV and fluorescence spectroscopic analysis, circular dichroism,
viscometry and isothermal calorimetry shows binding and interaction of harmalol with several natural
and synthetic nucleic acids, both DNA and RNA, of different motifs. Furthermore, apoptotic hallmarks
like internucleosomal DNA fragmentation, membrane blebbing, cell shrinkage, chromatin condensation,
change of mitochondrial membrane potential, comet tail formation and ROS (reactive oxygen species)
dependent cytotoxicity being analyzed in the harmalol treated cancer cells.
Conclusion: These results stating the therapeutic role of harmalol, will lead to the interesting knowledge
on the cytotoxicity, mode, mechanism, specificity of binding and correlation between structural aspects
and energetics enabling a complete set of guidelines for design of new drugs.