We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC₅₀ = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 μM), and efflux impaired E. coli strain (MIC = 0.78 μM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.

The amyloid-β peptide (Aβ) has been associated with Alzheimer’s disease (AD) for decades. The original amyloid cascade hypothesis declared that the insoluble extracellular plaques were responsible for Aβ toxicity. Later, this hypothesis has been updated and soluble intracellular Aβ forms and their effects within the cell have come into focus. Mitochondrial dysfunction plays an important role in the pathophysiology of AD. Aβ was detected inside mitochondria and several mitochondrial proteins were found to interact directly with Aβ. Such interactions can affect a protein’s function and cause damage to the mitochondria and finally to the whole cell. This review summarizes the current knowledge of mitochondrial proteins directly interacting with Aβ and discusses their significance for the development of therapeutics in the treatment of AD.

17β‐hydroxysteroid dehydrogenase (17β‐HSD10) is a multifunctional human enzyme with important roles both as a structural component and also as a catalyst of many metabolic pathways. This mitochondrial enzyme has important functions in the metabolism, development and aging of the neural system, where it is involved in the homeostasis of neurosteroids, especially in regard to estradiol, changes in which make it an essential part of neurodegenerative pathology. These roles therefore, indicate that 17β‐HSD10 may be a possible druggable target for neurodegenerative diseases including Alzheimer's disease (AD), and in hormone‐dependent cancer. The objective of this review was to provide a summary about physiological functions and pathological roles of 17β‐HSD10 and the modulators of its activity. image