Skip to Main content Skip to Navigation
Journal articles

Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross‐Linking Activity of a Transpeptidase of l,d Specificity

Abstract : The carbapenem class of β-lactams has been optimized against Gram-negative bacteria producing extended-spectrum β-lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment of tuberculosis as these drugs are potent covalent inhibitors of l,d-transpeptidases involved in mycobacterial cell wall assembly. The optimization of carbapenems for inactivation of these unusual targets is sought herein by exploiting the nucleophilicity of the C8 hydroxyl group to introduce chemical diversity. As β-lactams are structure analogs of peptidoglycan precursors, the substituents were chosen to increase similarity between the drug and the substrate. Fourteen peptido-carbapenems were efficiently synthesized. They were more effective than the reference drug, meropenem, owing to the positive impact of a phenethylthio substituent introduced at position C2 but the peptidomimetics added at position C8 did not further improve the activity. Thus, position C8 can be modified to modulate the pharmacokinetic properties of highly efficient carbapenems.
Document type :
Journal articles
Complete list of metadata

https://hal-univ-paris.archives-ouvertes.fr/hal-03689984
Contributor : Emmanuelle BRAUD Connect in order to contact the contributor
Submitted on : Tuesday, June 7, 2022 - 5:16:47 PM
Last modification on : Wednesday, June 8, 2022 - 2:56:47 PM

Links full text

Identifiers

Citation

Saidbakhrom Saidjalolov, Zainab Edoo, Matthieu Fonvielle, Louis Mayer, Laura Iannazzo, et al.. Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross‐Linking Activity of a Transpeptidase of l,d Specificity. Chemistry - A European Journal, Wiley-VCH Verlag, 2021, 27 (10), pp.3542-3551. ⟨10.1002/chem.202004831⟩. ⟨hal-03689984⟩

Share

Metrics

Record views

0