20.500.12556/RUL-165967 Structural aspects of Mycobacterium tuberculosis DNA gyrase targeted by novel bacterial topoisomerase inhibitors In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of Mycobacterium tuberculosis DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of M. tuberculosis DNA gyrase in complex with DNA and compound 5 from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound 5 is a promising M. tuberculosis DNA gyrase inhibitor, with an IC$_{50}$ for M. tuberculosis gyrase of 0.096 μM, and it has potent activity against M. tuberculosis, with an IC$_{50}$ of 0.165 μM. NBTIs DNA gyrase M. tuberculosis crystal structure bifurcated halogen bonds DNA giraza Mycobacterium tuberculosis inhibitorji bakterijske topoizomeraze farmacevtska kemija tuberkuloza true false true Angleški jezik Slovenski jezik Članek v reviji 2024-12-16 11:46:33 2024-12-16 11:46:36 2024-12-17 04:11:06 0000-00-00 00:00:00 2024 0 0 Str. 2164−2170 iss. 12 Vol. 15 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:616-002.5 1948-5875 10.1021/acsmedchemlett.4c00447 215946755 kokot-et-al-2024-structural-aspects-of-mycobacterium-tuberculosis-dna-gyrase-targeted-by-novel-bacterial-topoisomerase.pdf kokot-et-al-2024-structural-aspects-of-mycobacterium-tuberculosis-dna-gyrase-targeted-by-novel-bacterial-topoisomerase.pdf 1 F9AE93CDB8CB4E1CEA8BA539B1EA29F5 1a4b385003983a348facbced4e04950ef40759c0fb10fc9ebdf5be490de6c37a b37604a3-bb9a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=197300 https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00447 1 7e9c1b1e-bb9a-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=197299 Fakulteta za farmacijo 0 0 0