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Identification of ethyl-6-bromo-2((phenylthio)methyl)imidazo[1,2-a]pyridine-3-carboxylate as a narrow spectrum inhibitor of Streptococcus pneumoniae and its FtsZ
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-02-06 , DOI: 10.1016/j.ejmech.2024.116196 Kousar Jahan 1 , Rachana Rao Battaje 2 , Vidyadhar Pratap 2 , Ganesh Ahire 1 , Athira Pushpakaran 2 , Anvesh Ashtam 2 , Prasad V Bharatam 1 , Dulal Panda 3
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2024-02-06 , DOI: 10.1016/j.ejmech.2024.116196 Kousar Jahan 1 , Rachana Rao Battaje 2 , Vidyadhar Pratap 2 , Ganesh Ahire 1 , Athira Pushpakaran 2 , Anvesh Ashtam 2 , Prasad V Bharatam 1 , Dulal Panda 3
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Filamentous temperature-sensitive mutant Z (FtsZ) is a key cell-division protein recognized as an important target for anti-bacterial drug discovery, especially in the context of rising multi-drug resistance. A respiratory pathogen, , is rapidly evolving antibiotic resistance, thus posing a clinical risk in the developing world. Inhibiting the conserved protein FtsZ, leading to the arrest of cell division, is an attractive alternative strategy for inhibiting . Previously, Vitamin K3 was identified as an FtsZ-targeting agent against . In the present work, docking studies were used to identify potential anti-FtsZ agents that bind to the Vitamin K3-binding region of a homology model generated for FtsZ. Compounds with imidazo[1,2-]pyridine-3-carboxylate core were synthesized and screened for their anti-proliferative activity against . Remarkably, the hit compound - showed anti-bacterial action against without any activity on other bacteria. In , - showed similar inhibitory action on FtsZ and cell division as Vitamin K3. Sequence alignment identified three unique residues within FtsZ that - binds to, providing a structural basis for the observed specificity. - is one of the first narrow-spectrum agents identified against that targets FtsZ, and we present it as a promising lead for the design of narrow-spectrum anti-FtsZ anti-pneumococcal compounds
更新日期：2024-02-06
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