Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies

Abstract

<jats:sec> <jats:title>Background:</jats:title> <jats:p>Thiazolidinediones and its bioisostere, namely, rhodanines have become ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory were subjected to docking studies against PPAR-γ receptor for their selection.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results:</jats:title> <jats:p>As part of the synthesis of selected twelve glitazones, the core moiety, pyridine incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1 cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window, glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic activity.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Based on the glucose uptake results, structure activity relationships are drawn for the title compounds.</jats:p> </jats:sec>

Identification of benzothiazole‐rhodanine derivatives as α‐amylase and α‐glucosidase inhibitors: Design, synthesis, in silico, and in vitro analysis

“…Lipinski's rule of five is mainly used to verify molecular properties, 16 which are essential and related to pharmacokinetics (PK) of the drug molecule, carried out with Schrodinger 2020‐4 suite device Maestro 11.7.012 17 . Qikprop is rapid, precise, and accessible to predict absorption, distribution, metabolism and excretion (ADME) properties 18 .…”

Identification of Benzothiazole‒Rhodanine Derivatives as α-Amylase and α-Glucosidase Inhibitors: Design, Synthesis, In-silico and In-Vitro Analysis

“…The title compounds benzothiazole -rhodanine derivatives (A1-10), were prepared by Knoevenagel condensation where N-substituted rhodanines react with substituted aromatic aldehydes in toluene medium in presence of Piperdine and glacial acetic acid as catalysts. The key intermediate N-substituted rhodanines was obtained by the procedure reported previously [15], where a freshly prepared sodium chloroacetate solution was slowly added to the dithiocarbamate solution with stirring at 0-5°C, followed by successive cyclization with Con. HCl.…”

“…The formation of the product was monitored with the help of TLC and followed by cooling the reaction mixture. The precipitated compound is ltered, washed with water, and recrystallization was done using ethanol [15]. The physical data of compounds (A1-10) is given in Table-1 Lipinski's rule of ve is mainly used to verify molecular properties [19] which are essential and related to PK of the drug molecule, which is carried out with Schrodinger 2018-3 suite device Maestro 11.7.012 [20].…”

Identification of Benzothiazole‒Rhodanine Derivatives as α-Amylase and α-Glucosidase Inhibitors: Design, Synthesis, In-silico and In-Vitro Analysis

“…(FT-IR, 1 H NMR, 13 C NMR, HR-MS).The title compounds benzothiazole -rhodanine derivatives(A1-10),were prepared by Knoevenagel condensation where Nsubstituted rhodanines react with substituted aromatic aldehydes in toluene medium in presence ofPiperdine and glacial acetic acid as catalysts. The key intermediate N-substituted rhodanines was obtained by the procedure reported previously [15], where a freshly prepared sodium chloroacetate solution was slowly added to the dithiocarbamate solution with stirring at 0-5°C, followed by successive cyclization with Con. HCl.…”