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The interaction between the anti-cancer drug Palbociclib ( PAL ) and calf-thymus DNA (CT-DNA) was investigated using various biophysical techniques in a physiological buffer (pH 7.4). It was found that PAL intercalated into the base pairs of CT-DNA as evidenced from the results of UV-Vis, fluorescence, circular dichroism (CD), competitive binding assay with ethidium bromide (EB) and Hoechst 33258, KI quenching study, the effect of denaturing agent and viscosity measurements. The magnitude of binding constants (10 6 M -1 ) at different temperatures suggested strong binding between PAL and CT-DNA during complexation. The observed ΔH o > 0 and ΔS o > 0 indicated that the binding process is primarily driven by hydrophobic interactions. Molecular docking studies indicated partial intercalation of pyridopyrimidine ring between the base pairs of DNA. Free energy surface (FES) analysis derived from metadynamics simulation studies revealed the PAL -induced cleavage of DNA, which was confirmed by gel electrophoresis experiments.Communicated by Ramaswamy H. Sarma.

The induced fit docking of anilino quinoline scaffold results in the required hydrogen bonding interactions with amino acid residues in the orthosteric site of 3 Phosphoinositide dependent kinase (PDK1). The rational design of 4-substituted amino quinolines is carried out and eight compounds are synthesized. Four crystal structures are determined and their binding mode with adenosine triphosphate (ATP) site of PDK1 is analyzed. The anticancer activity in A549 cell lines of the test compounds by MTT assay resulted in an inhibitor with IC 50 value of 0.96 µM which is less than the pemetrexed, a marketed lung cancer drug., (Copyright © 2018 Elsevier Inc. All rights reserved.)