Survey of ACCase and ALS resistance in winter annual grasses identifies target-site and nontarget-site imazamox resistance in Secale cereale.

Background: Early detection of herbicide resistance in weeds is crucial for successful implementation of integrated weed management. We conducted a herbicide resistance survey of the winter annual grasses feral rye (Secale cereale), downy brome (Bromus tectorum), and jointed goatgrass (Aegilops cylindrica) from Colorado winter wheat production areas for resistance to imazamox and quizalofop.

Results: All samples were susceptible to quizalofop.

Exploration of the Structural Space in 4(3)-Quinazolinone Antibacterials.

We report herein the syntheses of 79 derivatives of the 4(3)-quinazolinones and their structure-activity relationship (SAR) against methicillin-resistant (MRSA). Twenty one analogs were further evaluated in in vitro assays. Subsequent investigation of the pharmacokinetic properties singled out compound (()-3-(5-carboxy-2-fluorophenyl)-2-(4-cyanostyryl)quinazolin-4(3)-one) for further study.

In Vitro Model of the Gram-Negative Bacterial Cell Envelope for Investigation of Anti-Infective Permeation Kinetics.

The cell envelope of Gram-negative bacteria is a formidable biological barrier, inhibiting the action of antibiotics by impeding their permeation into the intracellular environment. In-depth understanding of permeation through this barrier remains a challenge, despite its critical role in antibiotic activity. We therefore designed a divisible in vitro permeation model of the Gram-negative bacterial cell envelope, mimicking its three essential structural elements, the inner membrane and the periplasmic space as well as the outer membrane, on a Transwell setup.

CYP17A1-independent production of the neurosteroid-derived 5α-pregnan-3β,6α-diol-20-one in androgen-responsive prostate cancer cell lines under serum starvation and inhibition by Abiraterone.

CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone.

Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.

The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multidrug resistance (MDR) combined with complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods.