Khalid Mohammed Khan
University of Karachi, Pakistan
Diabetes mellitus is the most prevalent metabolic syndrome world-wide, characterized by hyperglycemia (increase in glucose level) resulting in various short-term metabolic changes in lipid and protein metabolism and long-term irreversible vascular changes. When proteins are exposed to elevated levels of glucose a series of non-enzymatic chemical reactions occur that lead to the gradual buildup of advanced glycation end products (AGEs) in body tissues that cause various complications in the body. Hyperglycemia, affects eyes (cataract), blood vessels (atherosclerosis), nerves (neuropathy), kidney (nephropathy) and cause impaired wound healing. Postprandial hyperglycemia is an independent risk factor for cardiovascular diseases. Non-enzymatic models for anti-glycation i.e., BSA-MG and enzymatic model α-glucosidase inhibition will be discussed. In glycation, reactive intermediate methyl glyoxal (MG) binds with amino acid more easily than its carbohydrate precursor. Serum albumin, 80% of blood protein, is more prone to non-enzymatic glycation. Inhibition of protein glycation due to hyperglycemia is therefore an important and attractive approach towards the prevention and management of late diabetic complications. Alpha-glucosidase is an enzyme responsible for the conversion of complex carbohydrates to glucose. Keeping this in view, our group is working for investigation of novel anti-glycating agents. Based on virtual screening results, we have synthesized several classes of compounds and evaluated them for their in vitro and in vivo α-glucosidase inhibitory potential and methyl glyoxal binding potential. All these interesting results will be discussed in detail during talk.
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