Two novel probes were designed, sharing the same BODIPY core but differing only by a minimized variation in the recognition site from 4-hydroxyaniline into 4-methoxyaniline. Such a small change in the reaction site could switch the selective detection from peroxynitrite to HOCl. Undoubtedly, the new designed BODIPY core exhibits valuable properties.

•A novel probe for HOCl was synthesized and evaluated.•HOCl-promoted rapid transduction of thioether to sulfoxide function.•This probe features a fast and ratiometric detection.•The probe works excellently within a pH range of 4–10.•This probe can be employed to image endogenous HOCl generation.A BODIPY-based ratiometric fluorescent probe for HOCl has been designed based on the transduction of thioether to sulfoxide function. This probe features a marked absorption and emission blue-shift upon the HOCl-promoted rapid transduction, enabling the highly selective and ratiometric detection. In addition, the probe works excellently within a wide pH range of 4–10, addressing the existing pH dependency issue. Living cells studies demonstrate that the probe is cell membrane permeable and can be employed successfully to image endogenous HOCl generation in macrophage cells.A novel thiol-sulfoxide transduction based probe for HOCl was synthesized and evaluated. This probe features fast response, ratiometric detection and pH-independent sensing.

Alzheimer’s disease (AD) is characterized by intracellular and extracellular protein aggregates, including microtubule-associated protein tau and cleavage product of amyloid precursor protein, β-amyloid (Aβ). Tissue transglutaminase (tTG) is a calcium-dependent enzyme that cross-links proteins forming a γ-glutamyl-ε-lysine isopeptide bond. Highly resistant to proteolysis, this bond can induce protein aggregation and deposition. We set out to determine if tTG may play a role in pathogenesis of AD. Previous studies have shown that tTG and isopeptide are increased in advanced AD, but they have not addressed if this is an early or late feature of AD. In the present study, we measured tTG expression levels and enzyme activity in the brains of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD, as well as a transgenic mouse model of AD. We found that both enzyme expression and activity were increased in MCI as well as AD compared to NCI. In the transgenic model of AD, tTG expression and enzyme activity increased sharply with age and were relatively specific for the hippocampus. We also assessed overlap of isopeptide immunoreactivity with neurodegeneration-related proteins with Western blots and found neurofilament, tau, and Aβ showed co-localization with isopeptide in both AD and transgenic mice. These results suggest that tTG might be a key factor in pathogenesis of abnormal protein aggregation in AD.

We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ (PPARγ) binding activities. Through the biological assays, compounds 18 and 38 were highlighted with Ki values of 12.15 nmol/L and 14.46 nmol/L, respectively. Then structure–activity relationship (SAR) was analyzed to screen privileged structural modifications. Moreover, molecular fitting of these compounds onto the approved drug Rosiglitazone in the PPARγ ligand binding domain was performed to elucidate the SAR and explore potential receptor–ligand interactions. These results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPARγ.A series of 2-thioxo-4-thiazolidinone derivatives was designed, synthesized and biologically evaluated for their PPARγ binding activities. We established a molecular docking based SAR model for PPARγ ligand binding domain.

•Three new steroidal glycosides were isolated from Marsdenia tenacissima.•All compounds were prepared and evaluated inhibitory activity against nitric oxide in RAW276.4 macrophages.•They exhibited weak inhibitory effects against nitric oxide (NO) at concentration 1 μM.Three new compounds 1–3 as C21 steroidal glycosides of diester derivatives of tenacigenin B were isolated from the ethanolic extract of stems of Marsdenia tenacissima. All compounds were prepared and evaluated inhibitory activity of nitric oxide in RAW276.4 macrophages. Compounds 1–3 exhibited inhibitory effects against nitric oxide (NO).

Sarsasapogenin, isolated from rhizomes of Anemarrhena asphodeloides, was found to be able to enhance memory. On the basis of the structure of Sarsasapogenin, a series of derivatives were synthesized and evaluated for their neuroprotective activity in PC12 cells and NO production inhibitory activity in RAW264.7 cell lines. The preliminary structure-activity relationship of them indicated that introduction of carbamate groups at the 3-hydroxyl position of sarsasapogenin might improve neuroprotective activity. Some synthesized derivatives such as AA3, AA4, AA9 and AA13 exhibited both notably neuroprotective activity and NO production inhibitory activity.

Two novel probes were designed, sharing the same BODIPY core but differing only by a minimized variation in the recognition site from 4-hydroxyaniline into 4-methoxyaniline. Such a small change in the reaction site could switch the selective detection from peroxynitrite to HOCl. Undoubtedly, the new designed BODIPY core exhibits valuable properties.