Yeni Urasil Türevi Organik Bir Molekülün Sentezi, Yapısal Hesaplamaları ve Moleküler Modelleme Çalışmaları

Urasil türevi yeni bir bileşik, (E)-5-((3-klor-2-hidroksibenziliden)amino)pirimidin-2,4 (1H,3H)-dion, sentezlendi ve spektroskopik yöntemler kullanılarak yapı tayini gerçekleştirildi. Molekülün DNA ile olan etkileşimi, bilgisayar destekli yöntemler ile araştırıldı ve oluk bağlayıcı olarak davranabileceği belirlendi. Bileşiğin, molekül orbitalleri ve kimyasal reaktivite parametreleri gibi fizikokimyasal özellikleri incelendi.

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

Anovel 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.

PDF

___

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.
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.
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.
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.
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. G. Parr, L. Szentpaly, S. Liu, Electrophilicity Index, J. Am. Chem. Soc.,121 (1999) 1922.
R. G. Pearson, The electronic chemical potential and chemical hardness, Journal of molecular Structure: Theochem, 255 (1992) 261.
A.D. Becke, Density functional thermochemistry III, The role of exact Exchange, J. Chem. Phys., 98, (1993), 5648-5652.
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).
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.
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.
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.
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.
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.
A. Hartwig, The role of DNA repair in benzene-induced carcinogenesis, Chem.-Biol. Interact., 184 (2010) 269- 272.
G. Bischoff, S. Hoffmann, DNA-Binding of Drugs Used in Medicinal Therapies, Current Medicinal Chemistry, 9 (2002) 321-348.