Alkaloids nucleic acid interactions

Physical Techniques for Alkaloid-Nucleic Acid Interaction. 167... 

Keywords Berberine Palmatine Coralyne Polymorphic nucleic acid structures Alkaloid-nucleic acid interactions... 

Protoberberine Alkaloid-Triplex Nucleic Acid Interaction. 194... 

Protoberberine Alkaloid-Nucleic Acid Quadruplex Interaction. 196... 

Appropriately designed biophysical studies can elucidate the mode(s), the binding affinities and the nature of the ligand-nucleic acid interaction that give rise to the observed selectivity and specificities. Thus, it is worthwhile to describe briefly the various physical techniques used to study alkaloid-DNA/RNA interactions. 

Interaction of Protoberberine Alkaloids with Nucleic Acid Structures. . . 176... 

Debnath D (1992) Physico-chemical studies on the interaction of isoquinoline alkaloids with nucleic acids. PhD Thesis, Calcutta Uuiversity... 

Das S (2000) Biophysical studies on the interaction of benzophenanthridine alkaloids with polymorphic nucleic acid structures. PhD Thesis, Jadavpim University... 

Pezzuto, J. M., Antosiak, S. K., Messmer, W. M., Slaytor, M. B. and Honig, G. R. 1983. Interaction of the antileukemic alkaloid, 2-hydroxy-3,8,9-trimethoxy-5-methylbenzo[c]phenanthridine (fagaronine) with nucleic acids. Chemistry and Biology Interaction, 43 323-339. 

Phase I and II clinical trials indicated that acronycine reduced pain of the spine in some patients with multiple myeloma [280,282,283]. Acronycine has been reported to cause leukopoenia and to have CNS-depressant activity [284], Biochemically, acronycine inhibits incorporation of extracellular nucleosides into the RNA and DNA of leukaemia L-5178Y cell culture. There is, however, no evidence of interaction between acronycine and DNA or inhibition of template activity of DNA. This alkaloid does not inhibit nucleic acid synthesis in the cell, but rather inhibits the accumulation of extracellular uridine or thymidine, as nucleotides, in the intracellular precursor pool [285, 286], Acronycine, acting primarily on membranous organelles [287], seems to interfere with the structure, function and/or turnover of cell membrane components, thereby changing the fluidity of the plasma membrane [288]. 

Ribosomal protein biosynthesis is often inhibited by alkaloids that interact with nucleic acids [23]. There are also more specific inhibitors, such as emetine. 

Berberine chloride exhibited reverse transcriptase inhibitory properties against both H1V-1RT (p66/p51)(Human immunodeficiency virus type 1 reverse transcriptaseXIC50 60.9 pg/ml [163.8 (J.M]) and HIV-2RT (p68/p55)(Human immunodeficiency virus type 2 reverse transcriptase)(IC o 57.8 pg/ml [155.5 pM]). The alkaloid is thought to inhibit various RNA and DNA polymerizing enzymes via interaction with nucleic acid template-primers [212]. 

Berberine chloride was evaluated for antimalarial activity against Plasmodium falciparum in vitro (two clones of human malaria Plasmodium falciparum D-6 [Sierra Leone clone] and W-2 (Indochina clone) and Plasmodium berghei in vivo (mice). The alkaloid exhibited an antimalarial potency equivalent to that of quinine in vitro, but was inactive in vivo. The results were consistent with those of others who have found berberine to be a potent inhibitor in vitro of both nucleic acid and protein biosynthesis in P. falciparum, and have demonstrated a strong interaction of berberine with DNA. In addition, the lack of in vivo antimalarial activity in mice observed with berberine and other protoberberine alkaloids agrees with clinical reports that have claimed berberine to be inactive as an antimalarial drug [228]. 

As compounds that are hydrophilic and basic, it is no surprise that alkaloids interact readily with essential biochemical constituents such as proteins, polysaccharides, and nucleic acids, forming hydrogen bonds and ionic bonds. Less obvious reactions may also be relatively common. For example, essential thiol groups of proteins can undergo nucleophilic reactions with positively charged alkaloids, and pi complexes are possible... 

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