Synthesis of Novel C3-Linked β-Carboline-Pyridine Derivatives Employing Khronke Reaction: DNA-binding Ability and Molecular Modeling Studies

Author(s): Nagula Shankaraiah, Pankaj Sharma, Srinivas Pedapati, Shalini Nekkanti, Vunnam Srinivasulu, Niggula Praveen Kumar, Ahmed Kamal.

Journal Name: Letters in Drug Design & Discovery

Volume 13 , Issue 4 , 2016

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Abstract:

A series of novel C3-linked β -carboline pyridine (BCP) derivatives have been synthesized via modified Khronke reaction and studied for their DNA-binding affinities. Among all the derivatives, compound 12f has shown significant enhancement in the DNA-binding affinity (ΔTm: 6.3 oC and 6.5 oC at 0 h and 18 h incubation) in comparison to the standard Doxorubicin (ΔTm: 2.4 oC and 2.6 oC at 0 h and 18 h incubation). This result suggested a strong intercalation with DNA double helix. Moreover, molecular modeling studies also showed that the planar β-carboline ring establishes π–π interactions with DNA base pairs and these interactions are further extended due to the presence of pyridine ring. The DNA intercalation has also been investigated for these compounds by molecular docking and the results are in agreement with thermal denaturation data.

Keywords: β-Carbolines, DNA-binding affinity, khronke reaction, DNA intercalation, molecular modeling, terpyridine.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2016
Page: [335 - 342]
Pages: 8
DOI: 10.2174/157018081304160303180050
Price: $58

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