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

Banerjee, Manas; Ghosh, M.; Pradhan, Sayantan; Sanmartín‐Matalobos, Jesús; Rej, Abhinandan; Hira, Sumit Kumar

doi:10.1021/acsabm.8b00775

Cited by 5 publications

(2 citation statements)

References 49 publications

(73 reference statements)

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“…[25] 6-Amino-1,3-dimethyl uracil-based azo derivatives and the essential pyrimidine core have shown potent anticancer property in murine lymphoma cancer cell lines. [26] Substituted alkylamino derivatives of uracil are used as GPR84 inhibitors. [27] Results and Discussion…”

Section: Introductionmentioning

confidence: 99%

“…Majority of uracil derivatives are used as inhibitors of acetylcholinesterase (AchE) and butyrlcholinesterase (BuCHe), the key molecules involved in Alzheimer's disease [25] . 6‐Amino‐1,3‐dimethyl uracil‐based azo derivatives and the essential pyrimidine core have shown potent anticancer property in murine lymphoma cancer cell lines [26] . Substituted alkylamino derivatives of uracil are used as GPR84 inhibitors [27] …”

Section: Introductionmentioning

confidence: 99%

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Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

et al. 2021

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With the far-flung importance of uracil and amides in innumerable fields of chemistry and biology, a coherent synthesis that nullifies the use of prodigal reagents, methods and catalysts are hugely accepted. From the present outcomes, we report a highly atom profitable nucleophilic addition reaction of aromatic aldehydes and heterocyclic amines for the generation of amides having an excellent yield and high reproducibility. The main force responsible for the forward reaction is the presence of the nitroso group at the C-5 position on uracil scaffold, which drives the formation of formidable range products. The conclusive mechanism is based on the dehydrogenation reaction of the carbinolamine product formed during the nucleophilic addition reaction of the aromatic aldehyde with the free heterocyclic amino group to yield the corresponding amides. The synthesized compounds were predicated for biological properties and proved it to be an ideal G protein-coupled receptor kinase2 (GRK2) inhibitor. Out of all, the compound 3 f showed the most preeminent properties when compared to Paroxetine, studied using molecular docking. At the same time, computed ADME analysis proved them as an ideal drug candidate. Our findings not only prophesize new methods for the synthesis of bioactive-amides using a cross-coupling strategy but also demonstrates their novel applications as a human GRK2 inhibitor.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

et al. 2021

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Design, Synthesis, and Biological Studies of C-5-Substituted Diazenyl Derivatives of Uracil as Potent and Selective Antileishmanial Agents Targeting Uridine Biosynthesis Pathway Enzymes

Das,

Kumar,

Kumar

et al. 2024

ACS Infect. Dis.

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Herein, we describe the design and synthesis of a series of C-5-substituted diazenyl derivatives of uracil, exhibiting selective and potent antileishmanial but not antibacterial or antifungal activity. The formation of the substituted derivatives was confirmed by using FTIR, 1 H, 13 C NMR, and HRMS analysis. Among all of the sets of tested compounds, only three [4a, 6b, and 8b] showed the highest activity against Leishmania donovani (LD) promastigote and amastigote models of LD infections. Further, the cytotoxicity assays performed using three different cell lines, Vero cells, J774 cells, and THP1 cells, along with erythrocyte hemolysis assay showed the highest biocompatibility for the 4a, making it a lead compound for further biological assays. The LD cell death associated with 4a was not linked with ergosterol depletion, a common mechanism of action of antileishmanial drugs like amphotericin B (AmB). However, the LD cell death in the presence of 4a was reversed significantly through supplementation of uridine monophosphate (UMP), indicating the specific role of uridine biosynthesis pathway as the target of 4a. Furthermore, the in silico studies predicted ornithine monophosphate decarboxylase enzyme (OMPDCase) from LD as the plausible target for 4a. The proteomics analysis showed stronger downregulation of the aforementioned OMPDCase and also for a few other enzymes that are involved in the UMP biosynthesis pathway. This indicates that OMPDCase and other enzymes that regulate the UMP biosynthesis may be the target of 4a. Overall, the C-5-substituted diazenyl derivatives of uracil are presented here as novel and potent antileishmanial agents that can be used for treating visceral leishmaniasis (VL) wherein at present drug resistance and side effects of existing drugs demand a look for safer alternatives.

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Tuning uracil derivatives for the AIE-based detection of pyrene at a nano-molar level: single-crystal X-ray structure and DFT support

Banerjee

Ghosh

et al. 2020

New J. Chem.

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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

Cited by 5 publications

References 49 publications

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

Direct Synthesis, Characterization and Theoretical Studies of N‐(6‐Amino‐1,3‐dimethyl‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐yl)benzamide Derivatives

Design, Synthesis, and Biological Studies of C-5-Substituted Diazenyl Derivatives of Uracil as Potent and Selective Antileishmanial Agents Targeting Uridine Biosynthesis Pathway Enzymes

Tuning uracil derivatives for the AIE-based detection of pyrene at a nano-molar level: single-crystal X-ray structure and DFT support

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