Synthesis and Biological Evaluation of Novel Uracil Derivatives as Thymidylate Synthase Inhibitors

Lone, Mohammad Nadeem; Gul, Shazia; Mehraj, Umar; Sofi, Shazia; Dar, Abid Hamid; Ganie, S. A.; Wani, Nissar Ahmad; Mir, Manzoor Ahmad; Zargar, Mohammed A.

doi:10.1007/s12010-023-04367-3

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…The reaction involved condensation of 5‐bromouracil 9 with various amines 10 a – i resulting in the formation of 5‐arylaminouracils 11 a – i which on further condensation with tetrakis(triphenylphospine)palladium and 6‐oxobicyclo[3.1.0]hex–2‐ene 12 yielded 5’‐norcarbocyclic derivatives 13 a – i (Scheme 4). The synthesised derivatives were evaluated for its antiviral activity against varicella‐zoster virus (VZV) and CMV and it was found that compound 13 b exhibited inhibitory activity against thymidine kinase (TK) deficient VZV strains (TK‐VZV) [37] and CMV with EC 50 of 48.89 μM, 76.47 μM and 40.90 μM respectively.…”

Section: Introductionmentioning

confidence: 99%

Uracil: A Pharmacophore with Diverse Biological Potential

Jain,

Sharma,

Utreja

2024

ChemistrySelect

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This review article delves into the intricate biological activities of uracil, an essential pyrimidine Base pivotal in RNA structures. Examining its involvement in nucleic acid metabolism, various multifunctional roles, spanning from influencing cell proliferation to its antimicrobial and antiviral properties. The study explores signal transduction pathways affected by uracil, unraveling potential therapeutic applications. By unraveling the nuanced biological mechanisms. This review contributes to a deeper understanding of uracil's impact, offering insights crucial for drug development and advancing biomedical research.

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Section: Introductionmentioning

confidence: 99%

Uracil: A Pharmacophore with Diverse Biological Potential

Jain,

Sharma,

Utreja

2024

ChemistrySelect

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“…Then, this cyclic phosphite is oxidized by iodine to generate the 5′-cyclic triphosphate, followed by hydrolysis to afford the UTP . In contrast, enzymatic synthesis offers an eco-friendly and efficient strategy for UTP production. , Schultheisz et al demonstrated the great potential of multienzymatic synthesis of UTP by reconstructing the de novo pyrimidine biosynthetic pathways, through expression, purification, and combination of up to 28 enzymes for product generation and cofactor recycling. However, the substantial work and cost involved in preparing this number of enzymes remain a significant obstacle to in vitro biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Multivariate Modular Metabolic Engineering for High Titer Uridine Triphosphate Production in Escherichia coli

Liu,

Chen,

et al. 2023

ACS Sustainable Chem. Eng.

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Uridine triphosphate (UTP) holds great potential for applications in the food and medicine fields. Compared with the chemical synthesis route, microbial biosynthesis of UTP through metabolic engineering approaches offers a sustainable and environmentally friendly alternative. However, the tightly regulated UTP metabolic pathway has presented challenges in building efficient microbial cell factories. To address this issue, we applied a modular metabolic engineering strategy to overcome four distinct bottlenecks in UTP production in Escherichia coli. First, by blocking the UTP catabolic module, we achieved a substantial accumulation of UTP up to 304.67 μM. Second, in the UTP synthetic module, a uridine 5′monophosphate (UMP) kinase variant (MtUMPK R141A/K148A ) was obtained based on crystal structure analysis, resulting in a 10.47-fold increase in catalytic capacity. Furthermore, by fusion expression of the UMP kinase variant and orotidine 5′phosphate decarboxylase, the conversion of UMP to UTP was improved, leading to UTP concentrations reaching 11.36 mM. Third, in the UTP precursor module, several key metabolism-related genes were engineered to enhance the supply of precursors, resulting in an 87.9% increase in UTP production. Finally, by implementing electron transport chain regulation with an ATP-sensing switch, the optimal strain E. coli K16 achieved an intracellular UTP concentration of 28.40 mM (13.75 g/L), which was 544.37-fold higher than that of the base strain. This study represents the design of a de novo UTP-producing strain through metabolic engineering, opening new avenues for UTP and its derivatives production.

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Visible light–driven organic synthesis under iridium (IrIII)-complex photocatalysis

Brahmachari

2025

Visible Light-Driven Organic Synthesis

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Synthesis and Biological Evaluation of Novel Uracil Derivatives as Thymidylate Synthase Inhibitors

Cited by 3 publications

References 42 publications

Uracil: A Pharmacophore with Diverse Biological Potential

Uracil: A Pharmacophore with Diverse Biological Potential

Multivariate Modular Metabolic Engineering for High Titer Uridine Triphosphate Production in Escherichia coli

Visible light–driven organic synthesis under iridium (IrIII)-complex photocatalysis

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