Intercalation of anticancer drug Palbociclib with calf-thymus DNA: new insights from molecular spectroscopic, molecular dynamic simulations and cleavage studies.

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 (106 M-1) at different temperatures suggested strong binding between PAL and CT-DNA during complexation. The observed ΔHo > 0 and ΔSo > 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.

[1]  F. Belal,et al.  Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib , 2022, Scientific Reports.

[2]  R. Priyadharshini,et al.  Multi-spectroscopic and free energy landscape analysis on the binding of antiviral drug remdesivir with calf thymus DNA. , 2022, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[3]  A. Khandar,et al.  Synthesis of ZnFe2O4@SiO2 nanoparticles as a pH-sensitive drug release system and good nano carrier for CT-DNA binding , 2021 .

[4]  G. Mahalakshmi,et al.  Spectroscopic Studies on the Interaction of Naphthyridines with DNA and Fluorescent Detection of DNA in Agarose Gel , 2021, Journal of fluorescence.

[5]  Yun-Shien Lee,et al.  Palbociclib induces DNA damage and inhibits DNA repair to induce cellular senescence and apoptosis in oral squamous cell carcinoma. , 2020, Journal of the Formosan Medical Association = Taiwan yi zhi.

[6]  N. Shahabadi,et al.  Evaluation of ct-DNA and HSA binding propensity of antibacterial drug chloroxine: Multi-spectroscopic analysis, atomic force microscopy and docking simulation. , 2020, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[7]  S. Salehzadeh,et al.  DNA binding and molecular docking studies of a new Cu(II) complex of isoxsuprine drug , 2019, Polyhedron.

[8]  A. Tiwari,et al.  New Near-infrared Fluorescent Probes with Single-photon Anti-Stokes-shift Fluorescence for Sensitive Determination of pH Variances in Lysosomes with a Double-Checked Capability. , 2018, ACS applied bio materials.

[9]  Md. Fazle Alam,et al.  In vitro DNA binding studies of therapeutic and prophylactic drug citral. , 2018, International journal of biological macromolecules.

[10]  Liang Chen,et al.  Dual cyclin‐dependent kinase 4/6 inhibition by PD‐0332991 induces apoptosis and senescence in oesophageal squamous cell carcinoma cells , 2017, British journal of pharmacology.

[11]  I. Naseem,et al.  Interaction of capsaicin with calf thymus DNA: A multi-spectroscopic and molecular modelling study. , 2017, International journal of biological macromolecules.

[12]  Laijin Tian,et al.  Synthesis and spectroscopic DNA binding investigations of dibutyltin N-(5-chlorosalicylidene)-leucinate , 2017 .

[13]  M. Shamsipur,et al.  Binding studies of the anti-retroviral drug, efavirenz to calf thymus DNA using spectroscopic and voltammetric techniques. , 2016, Luminescence : the journal of biological and chemical luminescence.

[14]  N. Shahabadi,et al.  Spectroscopic and computational studies on the interaction of DNA with pregabalin drug. , 2015, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[15]  Muhammad Arba,et al.  The binding modes of cationic porphyrin-anthraquinone hybrids to DNA duplexes: in silico study , 2015, Journal of biomolecular structure & dynamics.

[16]  Rongmei Kong,et al.  Studies on the interaction of apigenin with calf thymus DNA by spectroscopic methods. , 2015, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[17]  Guowen Zhang,et al.  Probing the binding mode of psoralen to calf thymus DNA. , 2014, International journal of biological macromolecules.

[18]  P. Puigserver,et al.  Cyclin D1-CDK4 Controls Glucose Metabolism Independently of Cell Cycle Progression , 2014, Nature.

[19]  S. Rehman,et al.  Naproxen intercalates with DNA and causes photocleavage through ROS generation , 2013, The FEBS journal.

[20]  N. Shahabadi,et al.  Study on the interaction of the drug mesalamine with calf thymus DNA using molecular docking and spectroscopic techniques. , 2013, Journal of photochemistry and photobiology. B, Biology.

[21]  N. Dharmaraj,et al.  Potentially cytotoxic new copper(II) hydrazone complexes: synthesis, crystal structure and biological properties. , 2013, Dalton transactions.

[22]  S. Kashanian,et al.  In vitro DNA binding studies of Aspartame, an artificial sweetener. , 2013, Journal of photochemistry and photobiology. B, Biology.

[23]  Fengli Qu,et al.  Spectroscopic analysis on the resveratrol-DNA binding interactions at physiological pH. , 2011, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[24]  Afaq Ahmad,et al.  Synthesis, crystal structure, antimicrobial activity and DNA-binding of hydrogen-bonded proton-transfer complex of 2,6-diaminopyridine with picric acid. , 2011, Journal of photochemistry and photobiology. B, Biology.

[25]  Zheng-yin Yang,et al.  Synthesis, Characterization, DNA Binding Properties, Fluorescence Studies and Antioxidant Activity of Transition Metal Complexes with Hesperetin-2-hydroxy Benzoyl Hydrazone , 2010, Journal of Fluorescence.

[26]  Guowen Zhang,et al.  Spectroscopic studies on the interaction of morin–Eu(III) complex with calf thymus DNA , 2009 .

[27]  Xiwen He,et al.  Characterization of the Binding of Methylene Blue to DNA by Spectroscopic Methods , 2000 .

[28]  Guowen Zhang,et al.  Intercalation of herbicide propyzamide into DNA using acridine orange as a fluorescence probe , 2015 .