Synthesis of novel mono and bis-indole conduritol derivatives and their α/β-glycosidase inhibitory effects

• Published in: Bioorganic & medicinal chemistry letters 2012-12, Vol.22 (24), p.7499-7503
• Main Authors: Çavdar, Hüseyin, Talaz, Oktay, Ekinci, Deniz
• Format: Article
• Language: English
• Subjects: Acarbose; Biological and medical sciences; Cancer; Conduritol; Diabetes mellitus; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glucosidase; Glycoside Hydrolases - antagonists & inhibitors; Glycoside Hydrolases - metabolism; Indole; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Infection; Inhibitor; Inositol - analogs & derivatives; Inositol - chemical synthesis; Inositol - pharmacology; lysosomal storage diseases; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.10.038

Here we synthesized four novel indole conduritol derivatives 1–4 for the first time in the literature and probed their biological activities with the α and β-glucosidases. The compounds showed quite effective glucosidase inhibitory action. IC50 values of the compounds were compared with the known glucosidase inhibitor acarbose and it was determined that newly synthesized indole conduritols had more powerful effect against β-glucosidase in addition to exhibiting moderate influence against α-glucosidase. Our molecules thus constitute an important starting point for the design and exploitation of novel glucosidase inhibitors since glucosidase inhibitors have widespread applications in the treatment of diabetes, viral infections, lysosomal storage diseases and cancers.