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Article Dans Une Revue Bioorganic and Medicinal Chemistry Letters Année : 2021

Synthesis of acyclic nucleoside phosphonates targeting Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis

Résumé

Flavin-Dependent Thymidylate Synthase (FDTS) encoded by ThyX gene was discovered as a new class of thymidylate synthase involved in the de novo synthesis of dTMP named only in 30 % of human pathogenic bacteria. This target was pursed for the development of new antibacterial agents against multiresistant pathogens. We have developed a new class of ANPs based on the mimic of two natural’s cofactors (dUMP and FAD) as inhibitors against Mycobacterium tuberculosis ThyX. Several synthetic efforts were performed to optimize regioselective N1-alkylation, cross-coupling metathesis and Sonogashira cross-coupling. Compound 19c showed a poor 31.8% inhibitory effect on ThyX at 200 μM.
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Dates et versions

hal-03322503 , version 1 (19-08-2021)

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Nicolas G Biteau, Vincent Roy, J.-C. Lambry, Hubert F Becker, Hannu Myllykallio, et al.. Synthesis of acyclic nucleoside phosphonates targeting Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis. Bioorganic and Medicinal Chemistry Letters, 2021, 46, pp.116351. ⟨10.1016/j.bmc.2021.116351⟩. ⟨hal-03322503⟩
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