Synthesis, Structural Calculations and Molecular Docking Studies of a Novel Uracil Derived Organic Molecule

Year 2018, Volume: 46 Issue: 3, 373 - 380, 01.09.2018

Gamze Koz

Abstract

A novel uracil derived compound, (E)-5-((3-chloro-2-hydroxybenzylidene)amino) pyrimidine-2,4(1H,3H)-
dione, was synthesized and characterized using spectroscopic techniques. The interaction of the molecule
with DNA was explored using computational methods which revealed that the molecule could act as a groove
binder. The physicochemical properties of the molecule such as frontier molecule orbitals and chemical reactivity
parameters were also investigated. 

Keywords

Uracil , Schiff base , DNA binding , groove binder , molecular modelling

References

• G. Bischoff, S. Hoffmann, DNA-Binding of Drugs Used in Medicinal Therapies, Current Medicinal Chemistry, 9 (2002) 321-348.
• A. Hartwig, The role of DNA repair in benzene-induced carcinogenesis, Chem.-Biol. Interact., 184 (2010) 269- 272.
• G. P. Mantle, V. F. Marquis, A. R. Manderville, B. Squillaci and A. Pfohl-Leszkowicz, Structures of Covalent Adducts between DNA and Ochratoxin A: A New Factor in Debate about Genotoxicity and Human Risk Assessment, Chem. Res. Toxicol., 23 (2010) 89-98.
• S. Kashanian, S. Askari, F. Ahmadi, K. Omidfar, S. Ghobadi and A. F. Tarighat, In Vitro Study of DNA Interaction with Clodinafop-Propargyl Herbicide, DNA Cell Biol., 27 (2008) 581-586.
• A. F. Tanious, Y. D. Ding, A. D. Patrick, R. R. Tidwell and D. W. Wilson, A New Type of DNA Minor-Groove Complex: Carbazole Dication−DNA Interactions, Biochemistry, 36 (1997) 15315-15325.
• F. Ahmadi and F. Bakhshandeh, In Vitro Study of Damaging Effects of 2,4-Dichlorophenoxyacetic Acid on DNA Structure by Spectroscopic and Voltammetric Techniques, DNA Cell Biol., 28 (2009) 527-533
• R. M. Shaker, M. A. Elrady, K. U. Sadek, Synthesis, reactivity, and biological activity of 5-aminouracil and its derivatives, Mol. Divers., 20 (2016) 153-183.
• M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, Jr. J. A. Montgomery, T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, O. D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. AlLaham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. C. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision C.02. Gaussian, Inc.,Wallingford CT. (2004).
• A.D. Becke, Density functional thermochemistry III, The role of exact Exchange, J. Chem. Phys., 98, (1993), 5648-5652.
• R. G. Pearson, The electronic chemical potential and chemical hardness, Journal of molecular Structure: Theochem, 255 (1992) 261.
• R. G. Parr, L. Szentpaly, S. Liu, Electrophilicity Index, J. Am. Chem. Soc.,121 (1999) 1922.
• O. Trott, A. J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31 (2010) 455.
• Y. Kaya, V. T. Yilmaz, T. Arslan, O. Buyukgungor, Experimental and theoretical DFT studies of structure, spectroscopic and fluorescence properties of a new imine oxime derivative, Journal of Molecular Structure, 1024 (2012) 65-72.
• T. J. Beaula, P. Muthuraja, M. Sethuram, M. Dhandapani, V.K. Rastogi, V. Bena Jothy, Biological and spectral studies of O-Tolyl Biguanide: Experimental and theoretical approach, J. Mol. Struct. 1128 (2017) 290.
• R. Satheeshkumar, R. Shankar, W. Kaminsky, S. Kalaiselvi, V.V. Padma, K.J.R. Prasad, Theoretical and experimental investigations on molecular structure of 7-chloro-9-phenyl-2,3-dihydroacridin-4(1H)-one with cytotoxic studies, J. Mol. Struct. 1109 (2016) 247.
• S. Jaime-Figueroa, A. Zamilpa, A. Guzma´n, D. J. Morgans,Jr., N-3-Alkylation of uracil and derivatives via N-1-boc protection, Synthetic Communications, 31 24 (2001) 3739-3746.