Ruthenium-Catalyzed C(sp2)-H Bond Bisallylation with Imidazopyridines as Directing Groups.

A Ru(II)-catalyzed bisallylation of imidazopyridines with vinylcyclopropanes or vinyl cyclic carbonate has been successfully realized. Notably, pharmacophore imidazopyridine was utilized as an intrinsic directing group, which gave access to value-added bisallylated products in high yields via double tandem C-H and C-C/C-O activation. The current methodology was featured with broad substrate scope, good functional group compatibility, and operational simplicity.

Temperature-Controlled Chalcogenation and Chalcogenocyanation of Imidazopyridines in Water under Transition Metal-Free Conditions.

A sustainable and transition metal-free approach for C3 chalcogenation and chalcogenocyanation of imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was performed in the presence of catalytic iodine in aqueous medium, which afforded either chalcogenated or chalcogenocyanated imidazopyridines under temperature control. The current protocol featured a broad substrate scope, transition metal-free and organic solvent-free conditions, operational convenience, and gram-scale production.

Non-peptide-based fluorogenic small-molecule probe for elastase.

Human neutrophil elastase (HNE) has been identified as a potential therapeutic target for the discovery of anti-inflammatory drugs for decades. However, little progress has been made on assays measuring the activity of HNE, especially on synthetic substrates which play essential role in determination of HNE activity. Herein, a small-molecule compound, 2,2,3,3,3-pentafluoro-N-(2-oxo-4-(trifluoromethyl)-2H-chromen-7-yl)-propanamide (compound 4), has been successfully designed as the first ever non-peptide-based fluorogenic substrate for HNE. A "turn-on" fluorometric assay based on 4 has been successfully developed for rapid determination of HNE activity and the inhibitory kinetic study. Most importantly, the probe 4 shows highly specific response for HNE among seven tested hydrolases or proteins and can be directly used to detect the elevated HNE activity in the serum of chronic obstructive pulmonary disease (COPD) patients compared to that of healthy controls. This specific and cost-effective probe will facilitate future high-throughput discovery of HNE inhibitors and clinical diagnosis of elastase-related diseases.

A simple, rapid method for simultaneous determination of multiple elements in serum by using an ICP-MS equipped with collision cell.

We developed an inductively coupled plasma mass spectrometry method for testing 23 elements, namely, Mg, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sn, Sb, Ba, W, Tl, Pb, and U, in human serum. The serum samples were analyzed after diluting 1/25 with 0.5% nitric acid, 0.02% Triton-X-100, and 2% methanol. Sc, In, Y, Tb, and Bi were assigned internal standards to correct the baseline drift and matrix interference. The kinetic energy discrimination mode of the instrument with helium gas as the collision gas eliminated polyatomic interference. All 23 elements exhibited excellent linearity in their testing range, with a coefficient of determination ≥ 0.9996. The limits of detection of the 23 elements were within the range of 0.0004-0.2232 µg/L. The intra- and inter-day precision (relative standard deviation) were < 12.19%. The recoveries of the spiked standard for all elements were 88.98-109.86%. Among the 23 elements of the serum reference materials, the measured results of Mg, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Se were within the specified range of the certificate, and the results of the other elements were also satisfactory. The developed method was simple, rapid, and effective, and only 60 µL sample was consumed. A total of 1000 serum samples from healthy individuals were randomly selected from the Henan Rural Cohort, which reflects the status of serum elements in rural adults from the Northern Henan province of central China.

Conjunctional Relationship between Serum Uric Acid and Serum Nickel with Non-Alcoholic Fatty Liver Disease in Men: A Cross-Sectional Study.

Serum uric acid (SUA) and heavy metals are closely related to non-alcoholic fatty liver disease (NAFLD). Yet, the conjunctional relationship between SUA and serum nickel (Ni) concentrations with the risk of NAFLD in men has not yet been investigated. Therefore, we designed this cross-sectional study to investigate the association of SUA or serum Ni with NAFLD in men. The cross-sectional study was based on data obtained from a prospective cohort study of common chronic non-communicable diseases in Central China, conducted in Xinxiang city, Central China's Henan Province, between April and June 2017. A total of 1709 male participants completed the physical examination. B-ultrasound was used to examine the liver and to diagnose NAFLD. Binary logistic regression models and restricted cubic splines were performed to estimate the association of the SUA and serum Ni with NAFLD. The prevalence of NAFLD among 1709 male participants was 46.6%. After adjusting for potential confounders, with the highest quartile compared to those with the lowest quartile, SUA (OR = 1.579, 95% CI: 1.140-2.189) and serum Ni (OR = 1.896, 95% CI: 1.372-2.625) were associated with NAFLD, respectively. At the same time, the associations for the second and third SUA quartiles were null. Restricted cubic splines showed a positive linear relationship between serum Ni (ln-transformed) and NAFLD risk. Intriguingly, high SUA and high Ni (OR = 2.370, 95% CI: 1.577-3.597) increased the risk of NAFLD, compared with those with low SUA and low Ni. Our findings demonstrate a positive linear trend between serum Ni concentrations and NAFLD risk. Men with elevated serum Ni had a higher risk of developing NAFLD when compared to those with high SUA. Furthermore, the conjunctional relationship of SUA and serum Ni with NAFLD risk was observed in men.

New NNN pincer copper complexes as potential anti-prostate cancer agents.

Eleven novel NNN Cu(II) complexes supported by a tridentate bis(imidazo[1,2-α]pyridin-2-yl)pyridine ligand were synthesized and characterized by elemental analysis, HRMS, and X-ray determination. Target prediction and docking studies indicated that these pincer complexes formed hydrogen bonds with Asp33 and Gly35 of Cathepsin D protein, which is highly associated with prognosis of advanced prostate cancer. Furthermore, they exhibited anti-proliferation activity in both androgen-sensitive and androgen-insensitive prostate cancer cells according to WST-1 assay results. Mechanistic study showed that pincer complexes arrested cell cycle progression at G0/G1 phase and inhibited Cathepsin D regulated signaling pathways. Most importantly, new pincer copper complexes significantly inhibited xenograft prostate cancer growth along with a promising in vivo safety profile. In summary, these results suggest the applicability of the developed novel pincer copper complexes as promising anticancer agents for prostate cancer treatment.