title: Poliothrysoside and its derivatives as novel insulin sensitizers potentially driving AMPK activation and inhibiting adipogenesis.
abstract: In our efforts to develop safe and active chemical entities from nature, we first identified poliothrysoside (1), a phytoconstituent isolated from Flacourtia indica, possessing antidiabetic potential. Subsequently, fifteen derivatives (2-16) were synthesized to assess the activity profile of this class. All the compounds were analyzed for their glucose uptake potency in chronic insulin-induced insulin resistant 3T3-L1 adipocytes. Interestingly, compound 2 exhibited strong ability to increase the insulin sensitivity, primarily activating the AMPK signaling pathway and also inhibited the adipogenesis in 3T3-L1 adipocytes, in concentration dependent manner. Overall, these studies suggest the potential of poliothrysoside and its derivatives as promising leads for non-insulin dependent type 2 diabetes (T2D).
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: kv_sashidhara@cdri.res.in.
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Suriya P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Salil
authors.initials: S
authors.lastname: Varshney
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Muheeb
authors.initials: M
authors.lastname: Beg
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
authors.forename: Anil N
authors.initials: AN
authors.lastname: Gaikwad
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007333:Insulin Resistance; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001565:Benzoates; D005960:Glucosides; D007004:Hypoglycemic Agents; C477961:poliothrysoside; D055372:AMP-Activated Protein Kinases
keywords: 3T3-L1 adipocytes; AMPK; Insulin resistance; Non-insulin dependent type 2 diabetes; Poliothrysoside