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Azouracil and Its Cu(II)-Catalyzed Cyclization to an Anticancer Active Triazole Derivative: Symmetrical and Asymmetrical Reductive Cleavage, DNA Interaction, and Molecular Docking Studies

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journal contribution
posted on 14.02.2019, 00:00 by Mahuya Banerjee, Milan Ghosh, Sayantan Pradhan, Jesús Sanmartín Matalobos, Abhinandan Rej, Sumit Kumar Hira, Debasis Das
The 6-amino-1,3-dimethyl uracil-based azo derivative (p-carboxy phenylazouracil, L11) undergoes Cu­(II)-catalyzed cyclization to a triazole derivative, namely, 1,3-dimethyl-8-(p-carboxy phenyl) azapurine (L11P). Interestingly, the azo functionality of L11 undergoes both symmetrical and asymmetrical reductive cleavage at two different reaction conditions. The chloride salts of Mn­(II), Ni­(II), and Pd­(II) catalyze reductive cleavage of an azo moiety in an asymmetric manner, producing a new uracil hydrazine derivative (A3). On the other hand, hydrazine catalyzes symmetrical reductive cleavage of the azo moiety of L11, resulting in 5,6-diamino-1,3-dimethyl uracil (A2) along with the starting p-aminobenzoic acid (A1). Time-dependent density functional theoretical (TD-DFT) studies provide optimized geometries of L11, L11P, and A3 along with their orbital energies. The L11 and L11P bind firmly to genomic DNA of E. coli with a site size n ∼ 9 and n ∼ 8. The L11P shows anticancer activity on selected murine lymphoma cancer cell lines (DL, YAC1, and 2PK3). In addition, its antiproliferative activity is measured with several cancer cell lines and found hemocompatible toward blood cells. Corresponding molecular docking studies of L11P with caspase-3 (cysteine-aspartic proteases) unlock their mode of interaction.