Rational Design, Synthesis and Evaluation of Novel Rodanine Derivatives for Antihyperglycemic Activity

• Published in: Polycyclic aromatic compounds Vol. 42; no. 4; pp. 1794 - 1805
• Main Authors: Mandal, Subhankar P., Reji, Anu, Bhavimani, Guru, Prabitha, P., Durai, Priya, Yuvaraj, S., Shashank, A., Krishna, K. L., Kumar, B. R. Prashantha
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 21.04.2022; Taylor & Francis Ltd
• Subjects: Antihyperglycemic activity; Chemical synthesis; Design; Dexamethasone; Dosage; Drug development; Glucose; glucose uptake activity; Hepatocytes; In vivo methods and tests; Insulin; Insulin resistance; MD simulation; molecular docking; Molecular modelling; NMR; Nuclear magnetic resonance; Peroxisome proliferator-activated receptors; Pioglitazone; PPAR-γ; rhodanines; Spectral analysis; Spectrum analysis
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2020.1808795

A new series of rhodanines with phenyl substitution at the fifth position of rhodanine ring were designed targeting the PPAR-γ receptor for their possible antihyperglycemic activity. The rational design and molecular modeling studies were performed against PPAR-γ (PDB ID: 2PRG). The compounds were docked and thereafter subjected for the synthesis via dithiocarbamate formation followed by Knoevenagel condensation. Structures were confirmed by IR, NMR and Mass spectral analysis. All synthesized compounds were screened for in vitro glucose uptake assay using isolated hepatocytes. The Compounds A5 and B5 having N-(p-methoxy benzyl) at third position of rhodanine ring showed good glucose uptake activity. These two compounds were further studied for the in vivo antihyperglycemic study against dexamethasone induced insulin resistance. The compounds were tested at single dose level of 10 mg/kg, per oral. The compound B5 showed significant antihyperglycemic activity when compared with the standard drug, pioglitazone. The illustration, about the molecular design, synthesis, analysis, glucose uptake study and in vivo antihyperglycemic activity is reported here along with the structure activity relationships. A series of N-Substituted rhodanines were synthesized by taking varied amines and aldehydes, via Knoevenagel condensation. The synthesized compounds were subjected to in vitro and in vivo glucose uptake assay. The compound showed comparable biological activity with reference to standard drug. Additionally, molecular docking and MD simulation study was performed to support the hypothesis.