The Structure-Antiproliferative Activity Relationship of Pyridine Derivatives.

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer's, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity.

Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity.

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Efficient and Sustainable Bidentate Amines-Functionalized Resins for Removing Ag+, Cu2+, Pb2+, and Fe3+ from Water.

We evaluate the effectiveness of chelating resins (CR) derived from Merrifield resin (MR) and 1,2-phenylenediamine (PDA), 2,2'-dipyridylamine (DPA), and 2-(aminomethyl)pyridine (AMP) as adsorbent dosimeters for Ag+, Cu2+, Fe3+, and Pb2+ cations from water under competitive and noncompetitive conditions. MR-PDA, MR-DPA, and MR-AMP were obtained in a 95-97% yield and characterized by IR, fluorescence, and SEM. The ability of CRs as adsorbents was determined by batch and flow procedures. MR-PDA showed a batch adsorption capacity order of Fe3+ (29.8 mg/g) > Ag+ (2.7 mg/g) > Pb2+ (2.6 mg/g) at pH 3.4. The flow adsorption showed affinity towards the Ag+ cation at pH 7 (18.4 mg/g) and a reusability of 10 cycles. In MR-DPA, the batch adsorption capacity order was Ag+ (9.1 mg/g) > Pb2+ (8.2 mg/g) > Cu2+ (3.5 mg/g) at pH 5. The flow adsorption showed affinity to the Cu2+ cation at pH 5 (2.2 mg/g) and a reuse of five cycles. In MR-AMP, the batch adsorption capacity was Ag+ (17.1 mg/g) at pH 3.4. The flow adsorption showed affinity to the Fe3+ cation at pH 2 (4.3 mg/g) and a reuse of three cycles. The three synthesized and reusable CRs have potential as adsorbents for Ag+, Cu2+, Fe3+, and Pb2+ cations and showed versatility in metal removal for water treatment.