title: Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs).
abstract: As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.
authors.affiliation: Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Vidadala Ramasubba
authors.initials: VR
authors.lastname: Rao
authors.forename: Puppala
authors.initials: P
authors.lastname: Muthenna
authors.forename: Gundeti
authors.initials: G
authors.lastname: Shankaraiah
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Akileshwari
authors.forename: Kothapalli Hari
authors.initials: KH
authors.lastname: Babu
authors.forename: Ganji
authors.initials: G
authors.lastname: Suresh
authors.forename: Katragadda Suresh
authors.initials: KS
authors.lastname: Babu
authors.forename: Rotte Sateesh
authors.initials: RS
authors.lastname: Chandra Kumar
authors.forename: Kothakonda Rajendra
authors.initials: KR
authors.lastname: Prasad
authors.forename: Potharaju Ashok
authors.initials: PA
authors.lastname: Yadav
authors.forename: J Mark
authors.initials: JM
authors.lastname: Petrash
authors.forename: Geereddy Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
authors.forename: Janaswamy Madhusudana
authors.initials: JM
authors.lastname: Rao
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001692:Biological Transport / Q000187:drug effects; D015195:Drug Design; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D062105:Molecular Docking Simulation; D031701:Piper / Q000737:chemistry*; D010881:Piperidones / Q000737:chemistry* / Q000302:isolation & purification; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013012:Sorbitol / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007211:Indoles; D010881:Piperidones; D010936:Plant Extracts; D011994:Recombinant Proteins; C498077:piperlongumine; D013012:Sorbitol; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase