pantetheinase inhibitors(Pfizer)

Three pairs of enantiomeric cinnamoyltriketone dimers, (+)‐ and (−)‐xanthochrysanthones A−C [(+)‐ and (−)‐1–3)], were recognized and obtained from Xanthostemon chrysanthus by employing the building blocks‐based molecular network (BBMN) strategy. Compounds 1–3 featured two new types of lobster‐shape carbon skeletons with unprecedented spiro[cyclohexane‐1,2′‐xanthene] or benzo[7,8]oxocino[4,5‐b]chromene tetracyclic ring systems. Their structures with absolute configurations were established by comprehensive spectroscopic analyses, X‐ray crystallography, and ECD calculations. Compounds 1–3 represent the first example of phloroglucinol derivatives that are biogenetically constructed by a De Mayo reaction followed by Michael addition. Additionally, compounds 1–3 exhibited significant antiviral activity against respiratory syncytial virus (RSV). Time‐of‐addition assays indicated that compound 3 specifically acts on the early stages of the virus replication process in RSV.

The development of precise diagnosis and the discovery of individualized drugs go together to provide effective therapy against inflammatory bowel disease (IBD). The exploitation of the unique imaging advantages of chemiluminescent probes represents a pivotal strategy for achieving this goal. Nevertheless, the dual-locked strategy, which is believed to enhance precision, is rarely employed in the design of chemiluminescent probes. A novel dual-locked chemiluminescent probe, BPan-CL, was designed based on IBD candidate biomarkers chymotrypsin (CHT) and vanin-1. BPan-CL exhibited specific reactivity and chemiluminescence response when subjected to simultaneous stimulation of CHT and vanin-1, with a signal-to-noise ratio superior to that of the fluorescent probe with the same dual-locked mode. In both live cell and IBD mice imaging, BPan-CL demonstrated superior sensitivity compared to its single-locked counterpart, Pan-CL. In contrast to Pan-CL, BPan-CL was able to more accurately identify IBD and healthy mice by in vivo imaging and allowed for early prediction of IBD using a noninvasive fecal test. BPan-CL has identified CHT and vanin-1 as valuable combinatorial biomarkers for accurate and early IBD diagnosis. This strategy has significant potential for use in biomedical imaging and future individualized therapies.