Tetrazoles as PPARγ ligands: A structural and computational investigation

Paula, Karina de; Santos, Jademilson Celestino dos; Mafud, Ana Carolina; Nascimento, Alessandro S.

doi:10.1016/j.jmgm.2021.107932

Cited by 1 publication

(1 citation statement)

References 71 publications

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“…In this experiment, hPPARγ-LBD was cloned into pET28a plasmid and transformed in BL21 DE3 Escherichia coli strain. A little later, the same authors investigated three isomeric tetrazole derivatives 44-46, structurally similar to thiazoldienones, using theoretical and experimental methods (Figure 9) [43]. According to the results obtained, all isomers are able to bind effectively to the PPARγ ligand binding domain, but the binding energy is still somewhat lower than for rosiglitazone 8.…”

Section: Peroxisome Proliferator-activated Receptors (Ppars) Agonistsmentioning

confidence: 98%

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents

Trifonov,

Ostrovskii

2023

IJMS

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Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces. In the present review, a systematic analysis of the activity of tetrazole derivatives against type 2 diabetes mellitus (T2DM) has been performed. As it was shown, the tetrazolyl moiety is a key fragment of many antidiabetic agents with different activities, including the following: peroxisome proliferator-activated receptors (PPARs) agonists, protein tyrosine phosphatase 1B (PTP1B) inhibitors, aldose reductase (AR) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, G protein-coupled receptor (GPCRs) agonists, glycogen phosphorylases (GP) Inhibitors, α-glycosidase (AG) Inhibitors, sodium glucose co-transporter (SGLT) inhibitors, fructose-1,6-bisphosphatase (FBPase) inhibitors, IkB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) inhibitors, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In many cases, the tetrazole-containing leader compounds markedly exceed the activity of medications already known and used in T2DM therapy, and some of them are undergoing clinical trials. In addition, tetrazole derivatives are very often used to act on diabetes-related targets or to treat post-diabetic disorders.

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Section: Peroxisome Proliferator-activated Receptors (Ppars) Agonistsmentioning

confidence: 98%