20.500.12556/RUL-135340 Computational design and development of benzodioxane-benzamides as potent inhibitors of FtsZ by exploring the hydrophobic subpocket Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This resistant strain is associated with a 64% increase in death compared to the antibiotic-susceptible strain. The prokaryotic protein FtsZ and the cell division cycle have been validated as potential targets to exploit in the general battle against antibiotic resistance. Despite the discovery and development of several anti-FtsZ compounds, no FtsZ inhibitors are currently used in therapy. This work further develops benzodioxane-benzamide FtsZ inhibitors. We seek to find more potent compounds using computational studies, with encouraging predicted drug-like profiles. We report the synthesis and the characterization of novel promising derivatives that exhibit very low MICs towards both methicillin-susceptible and -resistant S. aureus, as well as another Gram positive species, Bacillus subtilis, while possessing good predicted physical-chemical properties in terms of solubility, permeability, and chemical and physical stability. In addition, we demonstrate by fluorescence microscopy that Z ring formation and FtsZ localization are strongly perturbed by our derivatives, thus validating the target. gram positive-dependent diseases antibiotic-resistance MSSA MRSA Bacillus subtilis FtsZ Z ring FtsZ inhibition MIC pharmacology chemistry anti-bacterial agents methicillin-resistant Staphylococcus aureus drug resistance microbiology benzamides bacterial proteins veterinarska medicina true false true Angleški jezik Slovenski jezik Članek v reviji 2022-03-08 12:01:37 2022-03-08 12:01:38 2022-09-14 04:12:52 0000-00-00 00:00:00 2021 0 0 19 str. iss. 4, art. 442 Vol. 10 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 579:615.2:57.08 2079-6382 10.3390/antibiotics10040442 59812611 RAZ_Straniero_Valentina_2021.pdf RAZ_Straniero_Valentina_2021.pdf 1 52BE8E38131ACAF484AA6D5342CF4C56 b15c8477b73bafb20bc6b7aae6d32d5542b0cccd15d990216ed45bb9c34f08d6 15ad8cdf-9ecf-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154362 https://www.mdpi.com/2079-6382/10/4/442 1 d911f537-9ece-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154361 Fakulteta za farmacijo Veterinarska fakulteta 0 0 0