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Nanotechnology in Medicine: Drug Delivery Systems
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Elena Campano-Cuevas, Ana Mora-Boza, Gabriel Castillo-Dalí, AgustíN. RodríGuez-Gonzalez-Elipe, MaríA-Angeles Serrera-Figallo, Barranco Angel, Daniel Torres-Lagares
Initial recommendation for treating type 2 diabetes focuses on delaying disease progression through exercise and regulation of meals (Standards of Medical Care in Diabetes, 2013). Besides, treatment for type 2 diabetes includes oral hypoglycemic drugs, such as: sulfonylureas and repaglinide, that enhance INS secretion from the b-cells; troglitazone, that promotes the use of glucose by cells; metformin, that induces INS mechanism in liver tissue; and miglitol and acarbose that enact delayed carbohydrate absorption from food intake (Buse et al., 1999). However, in some cases other macromolecular diabetic such as Glucagon-like peptide (GLP) analogs like Exenatide and Liraglutide (Buse et al., 2009) must be injected subcutaneously due to the harsh environment of the gastrointestinal tract. The other major medications strategies constitutes combinational therapy of INS with sulfonylureas which reduced the daily requirement of INS (Riddle, 1996), INS and metformin combination therapy (Golay, 1995), and troglitazone-INS in combination to reduce INS requirement (Buse et al., 1998).
Biocatalyzed Synthesis of Antidiabetic Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Focusing on antidiabetic activity, Miglitol (Glyset™, Fig. 11.40, 117) is a commercial drug used for treating non-insulin dependent diabetes; the chemoenzymatic preparation of the carbohydrate core of this compound, 1-deoxynojirimycin 108 was reported in the late 1970s (Kinast and Schedel, 1978a; Kinast and Schedel, 1978b; Kinast and Schedel, 1981; Kinast et al., 1981), via a regioselective oxidation of the hydroxyl group at C-5 of N-CBz-1-amino-1-deoxysorbitol 115 using whole cells from Gluconobacter oxydans. More recently, a very similar procedure using the same microorganism, but starting from N-2-hydroxyethylglucamine 118 has been described (Zhang et al., 2011a). Considering the use of pure enzymes instead of whole cells, investigation of 1-deoxynojirimycin biosynthesis has led to the identification of Bacillus amyloliquefaciens genes gabT1, yktC1, and gutB1 as part of the overall azasugar biosynthetic pathway (Chen et al., 2007; Clark et al., 2011). These three genes, respectively, encode for transaminase, phosphatase and dehydrogenase activity, and based on these studies, very recently Wu et al. (Wu et al., 2014) have cloned zinc-dependent medium-chain NAD-dependent dehydrogenases from Bacillus amyloliquefaciens FZB42, Bacillus atrophaeus 1942, and Paenibacillus polymyxa SC2 and expressed them in BL21(DE3) Escherichia coli, describing the use of purified enzymes for producing nojirimycin and mannojyrimicin through a similar regioselective oxidation. Some chemoenzymatic synthesis of 1-deoxynojirimycin 108 and analogues via regioselective biooxidations.
Some of the organic ligand transition metal complexes can serve as potent α-glucosidase inhibitors: in-vitro, kinetics and in-silico studies
Published in Inorganic and Nano-Metal Chemistry, 2023
Syed Majid Bukhari, Rizwana Sarwar, Asma Zaidi, Majid Ali, Farhan A. Khan, Umar Farooq, Jalal Uddin, Aliya Ibrar, Ajmal Khan, Ahmed Al-Harrasi
The α-glucosidase is a membrane bound enzyme which is located in epithelium of the small intestine. It has vital importance in the functioning of carbohydrase and in digestion process of glycolipids, lyco-proteins and is involved in several other metabolic pathways.[1] It releases α-D-glucose (monosaccharide unit) by hydrolyzing non-reducing, terminal 1, 4-linked α-D-glucose (oligosaccharides and polysaccharides) to maintain postprandial blood glucose level.[2,3] The α-glucosidase inhibitors have been shown to possess therapeutic potential against type-2 diabetes mellitus, human immunodeficiency virus infection, obesity and metastatic cancer.[3–5] There are only three α-glucosidase inhibitors (acarbose, miglitol and voglibose) which are clinically used today for the treatment of type-2 diabetes. These inhibitors lower the rate of carbohydrase absorption and suppress postprandial hyperglycemia.[4]
In vitro antioxidant and enzyme inhibitory properties of Rubus caesius L
Published in International Journal of Environmental Health Research, 2019
Daniel Miroslaw Grochowski, Sengül Uysal, Gokhan Zengin, Michał Tomczyk
In the few past decades, the prevalence of global health problems like Alzheimer’s disease (AD), diabetes mellitus (DM), or obesity has dramatically increased in worldwide. For example, AD is the most common type of dementia in older adults and approximately 45 million people have AD worldwide (Wimo et al. 2017). Similarly, almost 500 million people are affected by diabetes in the world (Riyaphan et al. 2018). Taken together, urgent therapeutic cautions are required to fight these diseases. In these cautions, enzyme can play as one of valuable biological targets and this fact is also known as ‘key enzyme inhibitory theory’. According to this, the inhibition of key enzymes (cholinesterase for AD; glucosidase for DM and tyrosinase for hyperpigmentation problems) in the pathologies of these diseases could alleviate the symptoms (Kim and Uyama 2005; Etxeberria et al. 2012; Jamila et al. 2015). From this point, although some synthetic compounds (tacrine and donepezil for cholinesterase, miglitol and acarbose for glucosidase) can efficiently inhibit these enzymes, most of them have unpleasant side effects such as gastrointestinal disturbances or toxicity (Khan et al. 2018; Riyaphan et al. 2018). Taken together, the search for natural compounds possessing similar activities without the side effects attributed to synthetic compounds is one of the most important subject in scientific community.