20.500.12556/RUL-116752 Benzamide derivatives targeting the cell division protein FtsZ modifications of the linker and the benzodioxane scaffold and their effects on antimicrobial activity Filamentous temperature-sensitive Z (FtsZ) is a prokaryotic protein with an essential role in the bacterial cell division process. It is widely conserved and expressed in both Gram-positive and Gram-negative strains. In the last decade, several research groups have pointed out molecules able to target FtsZ in Staphylococcus aureus, Bacillus subtilis and other Gram-positive strains, with sub-micromolar Minimum Inhibitory Concentrations (MICs). Conversely, no promising derivatives active on Gram-negatives have been found up to now. Here, we report our results on a class of benzamide compounds, which showed comparable inhibitory activities on both S. aureus and Escherichia coli FtsZ, even though they proved to be substrates of E. coli efflux pump AcrAB, thus affecting the antimicrobial activity. These surprising results confirmed how a single molecule can target both species while maintaining potent antimicrobial activity. A further computational study helped us decipher the structural features necessary for broad spectrum activity and assess the drug-like profile and the on-target activity of this family of compounds. cell division protein FtsZ benzamide 1 4-benzodioxane 1 4-benzoxathiane multi-drug resistant Staphylococcus aureus Escherichia coli N43 veterinary medicine Staphylococcus aureus Escherichia coli veterinarska medicina true false true Angleški jezik Slovenski jezik Članek v reviji 2020-06-08 12:53:22 2020-06-08 12:53:23 2022-08-29 03:38:56 0000-00-00 00:00:00 2020 0 0 22 str. iss. 4, art. 160 Vol. 9 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 636.09:579 2079-6382 10.3390/antibiotics9040160 5042298 522975769 RAZ_Straniero_Valentina_2020.pdf RAZ_Straniero_Valentina_2020.pdf 1 53DF35B3A0CAF74858A9EE70C3658BA6 1165afd75b5b2d872a3c05dbba78f38bce29f82df3f6612ac554a85fd3404258 e6268e05-4dc7-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151427 https://www.mdpi.com/2079-6382/9/4/160 1 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=130428 Fakulteta za farmacijo Veterinarska fakulteta 0 0 0