EXPERIMENTAL AND COMPUTATIONAL STUDY OF BINDING INTERACTION OF ALKOXY DERIVATIVES OF N-ARYLHYDROXAMIC ACIDS WITH DNA

Authors

  • Bharati Verma School of studies in Chemistry Pt. Ravishankar Shukla university Raipur Chhattisgarh 492010, India
  • Manish Pardhi School of studies in Chemistry Pt. Ravishankar Shukla university Raipur Chhattisgarh 492010, India
  • Rama Pande School of studies in Chemistry Pt. Ravishankar Shukla university Raipur Chhattisgarh 492010, India

Keywords:

Fluorescence, Binding constant, Viscosity, Hydroxamic acid, Interaction with DNA

Abstract

Objective: Binding affinity towards DNA for small molecules is very important in the development of new therapeutic reagents. Interaction between N-Arylhydroxamic acid derivatives N-p-Tolyl-4-Ethoxybenzohydroxamic acid (p-TEBHA) and N-o- Tolyl-4-Ethoxybenzohydroxamic Acid (o-TEBHA), with calf thymus DNA (CT DNA) were studied by UV–visible absorption, fluorescence,  viscosity measurement and molecular docking.

Methods: The absorption and emission spectra of DMSO solution of hydroxamic acid derivatives were studied for their binding activity with calf-thymus DNA by titration with increasing amount hydroxamic acids. Docking was performed by HEX software.

Results: Fluorescent spectra showed that CT DNA quenches the emission spectra of p-TEBHA & o-TEBHA with binding constant 1.6 Ñ… 108 M-1 and 4.3 Ñ… 103 M-1 respectively. Competitive study with ethidium bromide (EB) indicates that p-TEBHA can displace the DNA-bound EB suggesting strong competition with EB whereas o-TEBHA does not displace the DNA-bounded Ethidium bromide effectively. UV study of the interaction of the complexes with calf-thymus DNA has shown that the hydroxamic acid derivatives can bind with CT DNA. The docking studies were used to predict the mode of interaction of the drug with DNA. It was observed that as far as binding strength was concerned the computational results complemented the experimental results.

Conclusion: Investigated hydroxamic acid derivatives are found to be strong DNA binders and seem to have promising drug like nature.

Downloads

Download data is not yet available.

References

Motlagh M K, Noroozifar M, Khmmarnia S. Fluorescence and DNA-binding spectral studies of neodymium (III) complex containing 2, 2-bipyridine, [Nd(bpy)2Cl3•OH2]. J Spectrochimica Acta Part A 2011;78:389–95.

Wang Q, Wang X, Yu Z, Yuan X, Jiao K. Spectroscopic and Electrochemical Studies on the Binding Mechanism of DNA with an Anthraquinone Biological Dye, Nuclear Fast Red. Int J Electrochem Sci 2011;6:5470-81.

Zhanga G, Guob J, Zhaob N, Wangb J. Study of interaction between kaempferol–Eu3+ complex and DNA with the use of the Neutral Red dye as a fluorescence probe. J Sens Actuat B 2010;144:239-46.

Zhang, Hu, X, Pan J. Spectoscopic Studies of the interaction between primicarb and calf thymus DNA. Guowen spectrochimica. J Acta Part A 2011;78:687-94.

Xia J, Chen C, Chen Z, Miele L, Sarkar F H, Wang Z. Targeting pancreatic cancer stem cells for cancer therapy. J Biochim Biophys Acta 2012;1826:385–399.

Wilson D M, Silverman L N, Bergauer M, Keshari K R. Solid phase synthesis of

Hydroxamate peptides for histone deacetylase inhibition. J Tetrahedron Let 2013;54:151–3.

Kwak SY, Yang JK, Choi HR, Park KC, Kim YB, Lee YS. Synthesis and dual biological effects of hydroxycinnamoyl phenylalanyl/prolyl hydroxamic acid derivatives as tyrosinase inhibitor and antioxidant. J Bioorg Med Chem Let 2013;23:1136-42.

Tegoni M, Remelli M. Metallacrowns of copper (II) and aminohydroxamates: Thermodynamics of self assembly and host guest equilibria. J Coord Chem Rev 2012;256:289– 315.

Samuni Y, Samuni U, Goldstein S. The use of cyclic nitroxide radicals as HNO scavengers. J Inorg Biochem 2012;1820:1560-6.

Zang H, Gates KS. DNA binding and alkylation by the ‘left half’ of azinomycin B. J Biochem 2000;39:14968-75.

Tiwari V, Pande R. Molecular Descriptors of Nâ€Arylhydroxamic Acids: A Tool in Drug Design. J Chem Biol Drug Des 2006;68:225–8.

Patre S, Thakur P, Pande R, Solubility and Hydrophobic Descriptors of N-Arylhydroxamic Acids. J Biosci Biochem Bioinfor 2011;1:267-70.

Vanjari H, Pande R, Hydroxamic acids: proton donor and acceptor strength for use in drug design. J Pharma Biomed Anal 2003;33:783-8.

Agrawal MA, Harjit J, Pande R. Base Strenth and solute-solvent Interaction of Metal Extractants: Hydroxamic Acids. J Acta Chimica Scand 1999;53:381-6.

Khare D, Pande R. Experimental and molecular docking study on DNA binding interaction of N-phenylbenzohydroxamic acid. J Der Pharma Chemica 2012;4:66-75.

Rajwade RP, Pande R, Mishra KP, Kumar A, Pandey BN. Hydroxamic Acids Analogous Against Breast Cancer Cells: 2Dâ€QSAR and 3Dâ€QSAR Studies. J QSAR Comb Sci 2009;28:1500-8.

Kumar A, Rajwade RP, Pandey BN, Pande R, Mishra KP. Mechanism of Apoptotic Death In Ehrlich Ascites Tumor Cells Induced By Derivatives of Hydroxamic Acid. J of Cell and Tissue Res 2007;7:943-8.

Rajwade RP, Pande R, Mishra KP, Kumar A, Pandey BN. Quantitative Structure-Activity Relationship (QSAR) of N-Arylsubstituted Hydroxamic Acids as Inhibitors of Human Adenocarinoma Cells A431. J Med Chem 2008;4:237-43.

Khare D, Verma B, Pande R. Antioxidant Activity of N-Phenylbenzohydroxamic Acid. Asian J Pharm Clin Res 2012;5:121-4.

Roshania R, Agrawal YK. Synthesis of N-Arylhydroxamic acids. J Chem Engg Data 1978;23:259-60.

Rajwade RP. Evaluation of lipophilicity, physical parameters and antitumor activity of N-arylsubstituted hydroxamic acids, Ph. D. Thesis Submitted to Pt. Ravishankar Shukla University, Raipur: Chhattisgarh India; 2002.

Agrawal YK, Tandon SG. Preparation and Properties of N-Arylhydroxamic acid. J Chem Engg Data 1971;16:371.

Gupta VK, Tondon SG. Studies on Hydroxamic Acids Preparation and Properties of N-I-naphthylhydroxamic Acids. J Chem Engg Data 1972;17:257.

Pande R, Tandon SG. Preparation and properties of N-arylhydroxamic acids. J Chem Engg Data 1979;24:72-4.

Shahabadi N, Heidari L. Binding studies of the antidiabetic drug, metformin to calf thymus DNA using multispectroscopic methods. J Spectrochimica Acta Part A 2012;97:406–10.

Satyanarayana S, Cabrowiak JC, Chaires JB. Tris (phenanthroline) ruthenium (11) Enantiomer Interactions with DNA: Mode and Specificity of Binding. J Biochem 1993;32:2573–84.

Arjmand F, Parveen S, Afzal M, Shahid M. Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper (II) benzimidazole complexes. J Photochem Photobio B: Bio 2012;114:15–26.

Selvi PT, Evans HS, Palanaindavar M. Synthesis, structure and DNA interaction of cobalt(III)bis-complexes of 1,3-bis(2-pyridylimino)isoindoline and 1,4,7-triazacyclononane. J Inorg Biochem 2005;99:2110–8.

Tabassum S, Afzal M, Arjmand F. New heterobimetallic Cu (II)-Sn2 (IV) complex as potential topoisomerase I inhibitor: in vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines. J Photochem Photobio B: Bio 2012;11:63–72.

Selvakumar B, Rajendiran V, Maheswari PU, Stoeckli-Evans H. Structure spectra and DNA-binding properties of mixed ligand copper (II) complexes of iminodiacetic acid, the novel role of diamine co-ligands on DNA formation and hydrolytic and oxidative double strand DNA cleavage. J Inorg Biochem 2006;100:316-30.

Mazzini S, Cristina Bellucci M, Mondelli R. Importance of the thiomorpholine introduction in new pyrrole derivatives as antimycobacterial agents analogues of BM 212. J Bioorg and Med Chem 2003;11:505–14.

Published

01-09-2014

How to Cite

Verma, B., M. Pardhi, and R. Pande. “EXPERIMENTAL AND COMPUTATIONAL STUDY OF BINDING INTERACTION OF ALKOXY DERIVATIVES OF N-ARYLHYDROXAMIC ACIDS WITH DNA”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 9, Sept. 2014, pp. 170-4, https://journals.innovareacademics.in/index.php/ijpps/article/view/1741.

Issue

Section

Original Article(s)