Design of Improved Antidiabetic Drugs: A Journey from Single to Multitarget Agents

• Published in: ChemMedChem 2022-12, Vol.17 (23), p.e202200320-n/a
• Main Authors: Tassopoulou, Vassiliki‐Panagiota, Tzara, Ariadni, Kourounakis, Angeliki P.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Antidiabetics; Arteriosclerosis; Atherosclerosis; Cardiovascular diseases; Design; diabetes; Diabetes Mellitus; drug design; Drug development; drug discovery; drug targets; Drugs; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Metabolic disorders; Metabolic syndrome; Movement disorders; multifactorial diseases; multitarget; Neurodegenerative diseases; Parkinson's disease; Pathogenesis; Pathophysiology; Pharmacology
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202200320

Multifactorial diseases exhibit a complex pathophysiology with several factors contributing to their pathogenesis and development. Examples of such disorders are neurodegenerative (e. g. Alzheimer's, Parkinson's) and cardiovascular diseases (e. g. atherosclerosis, metabolic syndrome, diabetes II). Traditional therapeutic approaches with single‐target drugs have been proven, in many cases, unsatisfactory for the treatment of multifactorial diseases such as diabetes II. The well‐established by now strategy of multitarget drugs is constantly gaining interest and momentum, as a more effective approach. The development of pharmacomolecules able to simultaneously modulate multiple relevant‐to‐the‐disease targets has already several successful examples in various fields and has, as such, inspired the design of multitarget antidiabetic agents; this review highlights the design aspect and efficacy of this approach for improved antidiabetics by presenting several examples of successful pharmacophore combinations in (multitarget) agents that modulate two or more molecular targets involved in diabetes II, resulting in a superior antihyperglycemic profile. A comprehensive yet selective overview of the design and development of multitarget agents that modulate two or more molecular targets involved in DT2 is provided. The recent examples presented, derived by multiple pharmacophore combinations, have a superior pharmacological/anti‐hyperglycemic activity profile.