دانلود کتاب مهارکننده های آلفا گلوکوزیداز – نامزدهای امیدوارکننده بالینی برای کشف داروی ضد دیابت

Diabetes mellitus is a growing global problem in both clinical and economic terms. The disease has been alarmingly ushering clinicians, healthcare authorities, and scientists into finding new avenues to curb its devastating impact on patients and healthcare systems. Consequently, the field of antidiabetic drug discovery has flourished dramatically in recent years witnessing development of promising drugs with broad spectra of modes of action. However, treatment of diabetes mellitus by oral α-glucosidase inhibitors is still confined to acarbose, miglitol, and voglibose. The drug development of antidiabetic α-glucosidase inhibitors is essentially at halt since acarbose, miglitol and voglibose were launched three decades ago. Healthcare authorities and pharmaceutical companies in many countries are phasing them out partly because of their efficacy problems, unwanted gastrointestinal side effects, lack of multiple modes of action, and lack of promising net therapeutic effects including improvement in quality of life. This does not mean that α-glucosidase inhibitor discovery has stopped; the scientific literature has been witnessing thousands of compounds of natural and synthetic origins exhibiting promising antihyperglycemic and α-glucosidase inhibitory activities. Therefore, there is ample supply of new compounds generating a plethora of α-glucosidase inhibitors simply piling up in the haystack of publications and reports that usually do not undergo further studies involving lead optimization and development. Realizing the gaps and vacuum in antidiabetic α-glucosidase inhibitor drug development, this book addresses the concern by finding “needles” in that ever growing haystack of compounds by identifying promising α-glucosidase inhibitors and presenting them to the drug development community to come forward and further gauge their potential candidacy for lead optimization, preclinical or even clinical trials. The book will serve as a valuable tool for biochemists, synthetic and medicinal chemists, enzymologists, pharmacologists, structural and computational biologists, and pharmaceutical companies who have interest or would like to direct their interest toward developing new α-glucosidase inhibitors as antidiabetic drugs. For this purpose, the groundwork for identifying promising inhibitors is already laid in the present work so that the target audience does not have to go through that tedious process of selecting lead inhibitors. New, safer and efficacious α-glucosidase inhibitors may be just around the corner, if reexplored. This work identifies 390 promising α-glucosidase inhibitors of natural and synthetic origins that may qualify for antidiabetic drug candidacy based on their enzyme kinetic data, potency of inhibition, ability to reduce blood glucose levels in vivo, and computational and structural biology. The book is composed of seven chapters that discuss a wide range of α-glucosidase inhibitors of diverse chemistry encompassing sugar mimics, polyphenols, terpenoids and steroids, azoles and cyclitols. It also addresses the general problems associated with drug development with special focus on relevant background and factors which are potentially responsible for challenges in the α-glucosidase drug development. The book discusses acarbose, miglitol and voglibose against a broader perspective of current antidiabetic drugs, and identifies supporting and contrasting avenues that provide insights into the future of α-glucosidase inhibitor drug discovery.