Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships

Kumar, B. R. Prashantha; Baig, Nasir R.; Sudhir, Sai; Kar, Koyal; Mandava, Kiranmai; Pankaj, Madhu; Nanjan, M. J.

doi:10.1016/j.bioorg.2012.08.002

Cited by 34 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glitazones contain a thiazolidine-2,4-dione nucleus to which the linker 1 is attached at the fifth position . Generally, thiazolidinedione derivatives act as strong/full PPARγ agonists.…”

Section: Activation Of Pgc-1α Via Pparγ Agonismmentioning

confidence: 99%

Glitazones Activate PGC-1α Signaling via PPAR-γ: A Promising Strategy for Antiparkinsonism Therapeutics

Prabitha

Justin

Kumar

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Understanding various aspects of Parkinson's disease (PD) by researchers could lead to a better understanding of the disease and provide treatment alternatives that could significantly improve the quality of life of patients suffering from neurodegenerative disorders. Significant progress has been made in recent years toward this goal, but there is yet no available treatment with confirmed neuroprotective effects.Recent studies have shown the potential of PPARγ agonists, which are the ligand activated transcriptional factor of the nuclear hormone superfamily, as therapeutic targets for various neurodegenerative disorders. The activation of central PGC-1α mediates the potential role against neurogenerative diseases like PD, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Further understanding the mechanism of neurodegeneration and the role of glitazones in the activation of PGC-1α signaling could lead to a novel therapeutic interventions against PD. Keeping this aspect in focus, the present review highlights the pathogenic mechanism of PD and the role of glitazones in the activation of PGC-1α via PPARγ for the treatment of neurodegenerative disorders.

show abstract

“…Glitazones contain a thiazolidine-2,4-dione nucleus to which the linker 1 is attached at the fifth position . Generally, thiazolidinedione derivatives act as strong/full PPARγ agonists.…”

Section: Activation Of Pgc-1α Via Pparγ Agonismmentioning

confidence: 99%

Glitazones Activate PGC-1α Signaling via PPAR-γ: A Promising Strategy for Antiparkinsonism Therapeutics

Prabitha

Justin

Kumar

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The peak of C4 appeared as a doublet by the coupling of H β at 180.8 ppm, and the 3 J (C4-Hβ) value was 5.6 Hz, implying that the derivative has ( Z )-geometry. The ( Z )-isomer is thermodynamically more stable than the corresponding ( E )-isomer because of the steric factor between the carbonyl group and phenyl ring and an intramolecular hydrogen bond between the oxygen of the carbonyl group and the vinylic H β [ 21 , 22 ]. Additionally, the peak of H β in the 1 H NMR spectrum appeared downfield (7.48–7.83 ppm) due to the anisotropic effect of the carbonyl group.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects

et al. 2023

View full text Add to dashboard Cite

In this study, (Z)-2-(benzylamino)-5-benzylidenethiazol-4(5H)-one (BABT) derivatives were designed as tyrosinase inhibitors based on the structure of MHY2081, using a simplified approach. Of the 14 BABT derivatives synthesized, two derivatives ((Z)-2-(benzylamino)-5-(3-hydroxy-4-methoxybenzylidene)thiazol-4(5H)-one [7] and (Z)-2-(benzylamino)-5-(2,4-dihydroxybenzylidene)thiazol-4(5H)-one [8]) showed more potent mushroom tyrosinase inhibitory activities than kojic acid, regardless of the substrate used; in particular, compound 8 was 106-fold more potent than kojic acid when l-tyrosine was used as the substrate. Analysis of Lineweaver–Burk plots for 7 and 8 indicated that they were competitive inhibitors, which was confirmed via in silico docking. In experiments using B16F10 cells, 8 exerted a greater ability to inhibit melanin production than kojic acid, and it inhibited cellular tyrosinase activity in a concentration-dependent manner, indicating that the anti-melanogenic effect of 8 is attributable to its ability to inhibit tyrosinase. In addition, 8 exhibited strong antioxidant activity to scavenge 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and peroxynitrite and inhibited the expression of melanogenesis-associated proteins (tyrosinase and microphthalmia-associated transcription factor). These results suggest that BABT derivative 8 is a promising candidate for the treatment of hyperpigmentation-related diseases, owing to its inhibition of melanogenesis-associated protein expression, direct tyrosinase inhibition, and antioxidant activity.

show abstract

“…The acylated amines 2 were synthesized by treating substituted aromatic amines 1 with chloroacetyl chloride using dichloromethane as a solvent. The acylated amines were then linked to eugenol in presence of anhydrous potassium carbonate and dry acetone to obtain novel eugenol derivatives 20 (1A–D) ( Scheme 1 ). The characterization of the synthesized compounds was done by IR, 1 H-NMR, 13 C-NMR, and mass spectrometry.…”

Section: Resultsmentioning

confidence: 99%

Novel derivatives of eugenol as potent anti-inflammatory agents via PPARγ agonism: rational design, synthesis, analysis, PPARγ protein binding assay and computational studies

Anjum¹,

Shanmugarajan

Shivaraju

et al. 2022

RSC Adv.

View full text Add to dashboard Cite

show abstract

Discovery of novel glitazones incorporated with phenylalanine and tyrosine: Synthesis, antidiabetic activity and structure–activity relationships

Cited by 34 publications

References 46 publications

Glitazones Activate PGC-1α Signaling via PPAR-γ: A Promising Strategy for Antiparkinsonism Therapeutics

Glitazones Activate PGC-1α Signaling via PPAR-γ: A Promising Strategy for Antiparkinsonism Therapeutics

Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects

Novel derivatives of eugenol as potent anti-inflammatory agents via PPARγ agonism: rational design, synthesis, analysis, PPARγ protein binding assay and computational studies

Contact Info

Product

Resources

About