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

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

Volume: 13 Issue: 4

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

Affiliation:

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

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 (ΔT_m: 6.3 ^oC and 6.5 ^oC at 0 h and 18 h incubation) in comparison to the standard Doxorubicin (ΔT_m: 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.

Cite this article as:

Shankaraiah Nagula, Sharma Pankaj, Pedapati Srinivas, Nekkanti Shalini, Srinivasulu Vunnam, Kumar Praveen Niggula and Kamal Ahmed, Synthesis of Novel C3-Linked β-Carboline-Pyridine Derivatives Employing Khronke Reaction: DNA-binding Ability and Molecular Modeling Studies, Letters in Drug Design & Discovery 2016; 13 (4) . https://dx.doi.org/10.2174/157018081304160303180050