Here, based on the identification of androgapholide as a potential therapeutic treatment against cancer, Alzheimer's disease, diabetes, and multiple sclerosis, due to its ability to inhibit a signaling pathway in immune system function, the authors sought ways to optimize the natural product human systems by manipulating its chemical structure. Through the semisynthesis of a natural product along with computational studies, the authors developed an understanding of the kinetic mechanisms of andrographolide and semisynthetic analogs in the context of Michael additions.
Anticholinergics are used in treating asthma, a chronic inflammation of the airways. These drugs block human M1 and M2 muscarinic acetylcholine receptors, inhibiting bronchoconstriction. However, studies have reported complications of anticholinergic usage, such as exacerbated eosinophil production and worsened urinary retention. Modification of known anticholinergics using bioisosteric replacements to increase efficacy could potentially minimize these complications. The present study focuses on identifying viable analogs of anticholinergics to improve binding energy to the receptors compared to current treatment options. Glycopyrrolate (G), ipratropium (IB), and tiotropium bromide (TB) were chosen as parent drugs of interest, due to the presence of common functional groups within the molecules, specifically esters and alcohols. Docking score analysis via AutoDock Vina was used to evaluate the binding energy between drug analogs and the muscarinic acetylcholine receptors. The final results suggest that G-A3, IB-A3, and TB-A1 are the most viable analogs, as binding energy was improved when compared to the parent drug. G-A4, IB-A4, IB-A5, TB-A3, and TB-A4 are also potential candidates, although there were slight regressions in binding energy to both muscarinic receptors for these analogs. By researching the effects of bioisosteric replacements of current anticholinergics, it is evident that there is a potential to provide asthmatics with more effective treatment options.
In this article, the authors quantify fluctuations of primary proteins found within bovine milk across four stages of lactation. Critically, these findings bear great relevance to the nutritional support of calves as well as the varying severity of symptoms of lactose intolerance.
