Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs with reduced off-target activity (hERG IC 50 > 18 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC 50 = 1.02 μM) and topo IV (IC 50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED 50 ) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.

Commercial fragrant rapeseed oil (CFRO), from roasted and hot-pressed seeds, is enjoyed in China for its unique aroma. However, the characteristic of aroma-active compounds in CFRO is still unclear. In this study, a new odor monolithic material sorptive extraction method was established to trap volatiles from rapeseed oil. Thirty CFROs were investigated using this method coupled with gas chromatography–mass spectrometry. A total of 29 volatile compounds were identified by gas chromatography–olfactometry including pyrazines, alcohols, aldehydes, ketones, and sulfur compounds. Further, 2,5-dimethylpyrazine (peanut-like), 3-ethyl-2,5-dimethylpyrazine (roasted nut-like), dimethyl trisulfide (cabbage-like), 4-isothiocyanato-1-butene (pungent and pickle-like), butyrolactone (caramel-like), and benzyl nitrile (pungent and sulfur-like) are affirmed as the key odorants for the overall aroma of CFRO, owing to their odor activity values ≥1. This work provides a new insight on acquiring aroma-active compounds from rapeseed oil in a more time-effective process compared to conventional methods. Futhermore, this novel approach is applicable in the field of food flavor.

One drawback frequently associated with olefin metathesis-mediated peptide macrocyclization, the loss of side chain functionality at sites of ring closure, may be circumvented by incorporation of side chain functionality within the ring-closing olefin segments. This approach is demonstrated in the preparation of a macrocyclic Grb2 SH2 domain antagonist designed as a conformationally constrained beta-bend mimic.

Summary Flaxseed oil (FSO) has a distinct flavor among various types of vegetable oil. However, molecular information on FSO volatiles remains limited. In this study, a total of 60 compounds of FSO pressed from three main cultivars in Xinjiang, China, were tentatively identified and then semi‐quantified by the headspace solid phase micro‐extraction gas chromatography‐mass spectrometry (HS‐SPME‐GC‐MS) technique. Thirty of them were previously unknown as volatiles in FSO. These compounds could be categorized into eight groups (with the total numbers and numbers of new compounds per group between brackets): aldehydes (20; 10), ketones (7; 4), alcohols (13; 6), carboxylic acids (8; 3), esters (3; 1), alkanes (3; 3), heterocyclic compounds (4; 2), and other compounds (2; 1). Odor‐specific magnitude estimation (OSME) analysis revealed 53 aroma active compounds in three kinds of FSO in a consensus by using GC‐O, of which (E, E)‐2,4‐pentadienal (green, oily), (E, E)‐2,4‐heptadienal (sweet, hazelnut, woody), 5‐ethyldihydro‐2(3H)‐furanone (cereal‐like), 1‐hexanol (herbaceous, woody, green), acetic acid (sour, pungent, strong), and butyrolactone (sweet, caramel), perceived with high intensity (3.0, OSME values), and are therefore considered as major contributors to the characteristic FSO odor in Xinjiang, China. Practical applications: Volatile compounds, whether major or minor, are crucial to FSO quality. Some of them make no direct contribution to the aroma, could be of important help to understand the formation and degradation of the volatiles with significant contribution to aroma, and they may additionally provide useful quality markers. The flavor of FSO varies widely, depending on fruit variety, degree of fruit ripeness, environmental conditions, growing region, and techniques of processing and storage. Therefore, the present study might be useful to identify purity or blending of FSO and may provide information for the producing conditions and the origin of the basic raw material.