engleski

Synthesis, Cytostatic and Antibacterial Evaluations of N-4-benzoylcytosine–1, 2, 3-triazole and 7-deazapurine–1, 2, 3-triazole Hybrides

Cytosine and 7-deazapurine (pyrrolo[2, 3-d]pyrimidine) derivatives have a great role in medicinal chemistry and have shown rather marked antitumor, antiviral, antibacterial and antiinflammatory activities.[1-4] 7-deazapurines are an important class of compounds, structurally and chemically related to naturally nucleosides. In the last few years, several 7-deazapurine derivatives have been approved for the treatment of different diseases or are currently in phase I/II clinical trials.[1] As important pharmacophores, pyrrolo[2, 3-d]pyrimidine scaffold is being extensively investigated and many of such compounds resulted active as kinase inhibitors.[5] Herein we present the synthesis of novel N-4-benzoylcytosine–1, 2, 3-triazole and pyrrolo[2, 3-d]pyrimidine–1, 2, 3-triazole hybrides and their cytostatic and antibacterial evaluations. The novel N-1 propargylated and C-5 alkynylated N-4-benzoylcytosine derivatives were prepared by N-alkylation of pyrimidine bases and subsequent Pd-catalysed Sonogashira cross-coupling reaction, while C-6 substituted pyrrolo[2, 3-d]pyrimidine derivatives were afforded by in situ N-heteroannulation of C-5 alkynylated cytosines. Cytosine- and 7-deazapurine–1, 2, 3-triazole hybrides were obtained by click reaction with corresponding azides in the pressence of CuI and base. The novel compounds were evaluated against tumor cell lines (HeLa, CaCo-2, Raji and K562) and on the growth of gram-positive and gram-negative bacterial strains. [1] F. Musumeci et al, Eur. J. Med. Chem. 2017, 127, 369. [2] L. Wang et al, J. Med. Chem. 2015, 58, 6938. [3] V. P. Kumar et al, Bioorg. Med. Chem. Lett. 2013, 23, 5426. [4] K. M. H. Hilmy et al, J. Am. Sci., 2011, 7, 308. [5] T. Wang et al, Bioorg. Med. Chem. Lett. 2016, 26, 2936.

Cytosine, 7-deazapurine, 1, 2, 3-triazole hybrides, cytostatic evaluations, antibacterial evaluations, click chemistry, Sonogashira cross-coupling reaction

nije evidentirano