Spectroscopic Evidence of Phosphorous Heterocycle–DNA Interaction and its Verification by Docking Approach
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In the present work, the interaction of phosphorous heterocycle (PH) with calf thymus DNA (CTDNA) has been studied using spectroscopy and verified by molecular modeling which is found to be in consonance with each other. Apparent association constant (Kapp = 4.77 × 103 M− 1), calculated using UV–Vis spectra indicating an adequate complex formation between CTDNA and PH. A dynamic mode of the fluorescence quenching mechanism in case of ethidium bromide (EB) + CTDNA by PH has been observed confirming formation of DNA-PH complex. A moderate binding constants of PH with CTDNA + EB has been observed (2.74 × 104 M− 1 at 293 K) by means of fluorescence data. Calculated values of thermodynamic parameters enthalpy change (ΔH) and entropy change (ΔS), suggests weak (van der Walls like) force and hydrogen bonds playing the main role in the binding of PH to CTDNA. Furthermore, the results of circular dichroism (CD) reveal that PH does not disturb native conformation of CTDNA. As observed from absorption and fluorescence spectroscopy the binding mode of PH with DNA was indicative of a non-intercalative binding, which was supposed to be a groove binding. The molecular modeling results show that PH is capable of binding DNA having docking binding energy = -7.26 kcal × mol− 1. Above mentioned experimental results are found to be in consonance with molecular docking simulations and supports the CTDNA-PH binding.
KeywordsCTDNA PH Spectroscopy Interaction Docking
Authors are thankful to Department of Science and Technology (DST) project (No. SB/S2/CMP-012-2014) for fellowship also SIC facility of Indian Institute of Technology Indore for the instrumentation facility. Authors greatly acknowledge Professor K.C. Majumdar and Dr. R. K. Nandi, University of Kalyani for providing phosphorous heterocycles compounds used in the present study.
- 3.Jw L (1988) Lexitropsins: rational design of DNA sequence reading agents as novel anti-cancer agents and potential cellular probes. Anticancer Drug Des 3:25–40Google Scholar
- 4.Kundu P, Ghosh S, Chattopadhyay N (2015) Exploration of the binding interaction of a potential nervous system stimulant with calf-thymus DNA and dissociation of the drug–DNA complex by detergent sequestration. Phys Chem Chem Phys 17:17699–17709. https://doi.org/10.1039/C5CP02101D CrossRefPubMedGoogle Scholar
- 11.Ganguly A, Ghosh S, Guchhait N (2015) Spectroscopic and viscometric elucidation of the interaction between a potential chloride channel blocker and calf-thymus DNA: the effect of medium ionic strength on the binding mode. Phys Chem Chem Phys 17:483–492. https://doi.org/10.1039/C4CP04175E CrossRefPubMedGoogle Scholar
- 19.Das A, Thakur R, Dagar A, Chakraborty A (2014) A spectroscopic investigation and molecular docking study on the interaction of hen egg white lysozyme with liposomes of saturated and unsaturated phosphocholines probed by an anticancer drug ellipticine. Phys Chem Chem Phys 16:5368. https://doi.org/10.1039/c3cp54247e CrossRefPubMedGoogle Scholar
- 30.Boger DL, Fink BE, Hedrick MP (2000) Total Synthesis of Distamycin A and 2640 Analogues: A Solution-Phase Combinatorial Approach to the Discovery of New, Bioactive DNA Binding Agents and Development of a Rapid, High-Throughput Screen for Determining Relative DNA Binding Affinity or DNA Binding Sequence Selectivity. J Am Chem Soc 122:6382–6394. https://doi.org/10.1021/ja994192d CrossRefGoogle Scholar
- 31.Lee M, Rhodes AL, Wyatt MD et al (1993) GC base sequence recognition by oligoimidazolecarboxamide and C-terminus-modified analogs of distamycin deduced from circular dichroism, proton nuclear magnetic resonance, and methidiumpropylethylenediaminetetraacetate-iron(II) footprinting studies. Biochem 32:4237–4245. https://doi.org/10.1021/bi00067a011 CrossRefGoogle Scholar
- 44.Caruso F, Rossi M, Benson A et al (2012) Ruthenium–Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro. J Med Chem 55:1072–1081. https://doi.org/10.1021/jm200912j CrossRefPubMedGoogle Scholar