Synthesis, reactivity, and biological activity of 5-aminouracil and its derivatives

Abstract

The synthesis and reactions of 5-aminouracil and its derivatives are comprehensively reviewed. A brief survey of biological activities, especially chemotherapeutic and pharmacological properties, is also reported.

5-Aminouracil and other inhibitors of DNA replication induce biphasic interphase–mitotic cells in apical root meristems of Allium cepa

“…Considering the recognized effects of HU and its capacity to promote IM cells in onion root meristems (Żabka et al 2010 , 2012 ), our experiments were primarily aimed at establishing the extent to which similar outcomes may be produced by other drugs known to affect different aspects of DNA synthesis. As shown in Table 1 , a spectrum of inhibitors efficient in generating biphasic (IM) organization of cell nuclei (tested over a broad range of dilutions) included: 5-aminouracil (5-AU), a thymine antagonist that blocks DNA synthesis and binds as a third strand capable of forming triplex DNA structures through Hoogsteen hydrogen bonds (Shaker et al 2016 ), aphidicolin (APH), an inhibitor of DNA polymerase α (Yokoyama et al 2016 ), 5-fluorodeoxyuridine (FUdR), an inhibitor of thymidylate synthetase (Anderson et al 2016 ), methotrexate (MTX), a folic acid analog that inhibits purine and pyrimidine synthesis (Cutolo et al 2001 ), and cytosine arabinoside (Ara-C), which incorporates into DNA and inhibits DNA replication by forming cleavage complexes with topoisomerase I (Wang et al 2010 ). No induction of IM cells was detected in experimental series using excess of thymidine or 5-FU.…”

“…When considering the data from our experiments with EdU as a thymidine analog and the results obtained using 5-ethynyl uridine (5-EU) transcription assay, it is obvious that both DNA replication and transcription may perform their specific tasks efficiently and simultaneously using common DNA templates without mutual interference. Thus, irrespective of DNA mismatches formed by 5-AU located as a middle base of a triplex triad via Hoogsteen hydrogen bonds (Rana and Ganesh 2000 ; Shaker et al 2016 ), the replication and transcription processes must have retained their ability to perform essential functions in a highly coordinated manner, preventing potential conflicts, which are the main intrinsic source of genome instability (Helmrich et al 2011 ; García-Muse and Aguilera 2016 ). Correspondingly, it cannot be ruled out that the cellular response to 5-AU-induced RS includes rapid transcriptional activation of genes involved in DNA metabolism and in the mechanisms engaged in DNA damage repair systems.…”

Synthesis, characterization, fluorescence imaging, and cytotoxicity studies of a uracil‐based azo derivative and its metal complexes

“…The two nitrogen-hydrogen (NH) groups showed characteristic singlets at δ = 11.7 and 11.8 ppm, which remain unchanged in the complexes. [23] The hydroxyl proton of azo-enol form was observed as a singlet peak at δ = 15.22 ppm. [24] 13 C NMR spectra of the ligand and the corresponding metal complexes were recorded ( Figure S5 and S6) in DMSO-d 6 .…”

An Efficient Approach for the Synthesis of 1,2,3‐Triazole Moiety to Generate Uracil Molecular Architectures Through Cu‐Catalyzed Azide–Alkyne Cycloaddition

“…The design and synthesis of dendritic architectures through the click chemistry approach have been gaining great attention during the recent years . Click chemistry refers to Cu(I)‐catalyzed Huisgen 1,3‐dipolar cycloaddition of azide and alkyne to obtain 1,4‐disubstitued 1,2,3‐triazole under mild reaction conditions with excellent chemoselectivity and good yield .…”