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Synthesis of Novel 9-O-N-aryl/aryl–alkyl Amino Carbonyl Methyl Substituted Berberine Analogs and Evaluation of DNA Binding Aspects

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Title Synthesis of Novel 9-O-N-aryl/aryl–alkyl Amino Carbonyl Methyl Substituted Berberine Analogs and Evaluation of DNA Binding Aspects
 
Creator Basu, Anirban
Jaisankar , P
Kumar, G Suresh
 
Subject Chemistry
 
Description This manuscript describes the design and synthesis of three 9-O substituted analogs of plant alkaloid berberine
to enhance the DNA binding affinity. Three analogs of berberine with aryl/aryl–alkyl amino carbonyl
methyl substituent at the 9-position of the isoquinoline chromophore were synthesized and
characterized by NMR (1HNMR and 13C NMR) and mass spectroscopy. The products were evaluated for
their binding to calf thymus DNA by a wide variety of techniques like spectrophotometry, spectrofluorimetry,
circular dichroism, thermal melting, viscosity and isothermal titration calorimetry. The results
revealed that these analogs showed more than six times higher binding affinity to DNA compared to berberine.
From fluorescence and absorbance studies it was inferred that all the analogs bound to DNA noncooperatively
in contrast to the cooperative binding of the parent alkaloid berberine. The viscosity and
ferrocyanide quenching experiments confirmed that the analogs are stronger intercalative binders to
DNA useful for potential biological applications. Stronger binding of the analogs was also inferred from
circular dichroism studies and thermal melting experiments. Thermodynamics of the binding from isothermal
titration calorimetry experiments revealed an entropy driven binding for these analogs compared
to the enthalpy driven binding of berberine. The small but negative heat capacity change of the
analogs along with the significant enthalpy–entropy compensation phenomenon observed established
the involvement of multiple weak noncovalent interactions in the binding process. A comparative study
also revealed that the spacer length is also significant in modulating the DNA binding affinities
 
Publisher Elsevier
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1496/1/BIOORGANIC_%26_MEDICINAL_CHEMISTRY__20(_8)2498%2D2505;2012[18].pdf
Basu, Anirban and Jaisankar , P and Kumar, G Suresh (2012) Synthesis of Novel 9-O-N-aryl/aryl–alkyl Amino Carbonyl Methyl Substituted Berberine Analogs and Evaluation of DNA Binding Aspects. Bioorganic & Medicinal Chemistry, 20 (8). pp. 2498-2505.
 
Relation http://dx.doi.org/10.1016/j.bmc.2012.03.006
http://www.eprints.iicb.res.in/1496/