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Therapeutic role of harmalol targeting nucleic acids: Biophysical perspective and in vitro cytotoxicity.
Mini Reviews in Medicinal Chemistry 2017 December 12
BACKGROUND: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is growing interest in search for anti-cancer drugs of plant origin with high efficacy, low toxicity and minimum side effects. Most of the chemotherapeutic agents due to their non-selective nature and dose limiting toxicity, 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 dependent cytotoxicity being analyzed in the harmalol treated cancer cells.
CONCLUSION: These results stating the therapeutic role of harmalol taken together will lead to 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.
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 dependent cytotoxicity being analyzed in the harmalol treated cancer cells.
CONCLUSION: These results stating the therapeutic role of harmalol taken together will lead to 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.
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