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Type 2 diabetes is characterized by hyperglycemia and a relative loss of β–cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin–nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α–amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA–IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β–cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes. [ABSTRACT FROM AUTHOR]

We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established. [ABSTRACT FROM AUTHOR]

Among the oldest marine species on the planet, the genus Salinispora is often encountered inhabiting sediments and other marine creatures in tropical and subtropical marine settings. This bacterial genus produces a plethora of natural products. The purpose of this study was to examine the potential for salinispora-based natural products (NPs) to combat the SARS-CoV-2 virus. The RCSB PDB was used to obtain the crystal structures of proteins 3CLpro and PLpro. All 125 NPs were obtained from online databases. Using Autodock Vina software v1.2.0 the molecular docking process was carried out after the proteins and ligands were prepared. Assessments of binding affinities and interacting amino acids were rigorously examined prior to MD simulations. The docking experiments revealed 35 NPs in total for both 3CLpro and PLpro, with high docking scores ranging from −8.0 kcal/mol to −9.0 kcal/mol. However, a thorough binding residue analyses of all docked complexes filtered nine NPs showing strong interactions with HIS: 41 and CYS: 145 of 3CLpro. Whereas, for PLpro, merely six NPs presented good interactions with residues CYS: 111, HIS: 272, and ASP: 286. Further research was conducted on residue–residue and ligand–residue interactions in both the filtered docked complexes and the Apo-protein structures using the Protein Contacts Atlas website. All complexes were found to be stable in CABS-flex 2.0 MD simulations conducted at various time frames (50, 125, 500, and 1000 cycles). In conclusion, salinaphthoquinone B appears to be the most promising metabolite, based on favorable amino acid interactions forming stable confirmations towards 3CLpro and PLpro enzymes, acting as a dual inhibitor. [ABSTRACT FROM AUTHOR]