Thiazolidinediones as antidiabetic agents: A critical review.
Bioorg Chem
; 77: 548-567, 2018 04.
Article
in En
| MEDLINE
| ID: mdl-29475164
ABSTRACT
Thiazolidinediones (TZDs) or Glitazones are an important class of insulin sensitizers used in the treatment of Type 2 diabetes mellitus (T2DM). TZDs were reported for their antidiabetic effect through antihyperglycemic, hypoglycemic and hypolipidemic agents. In time, these drugs were known to act by increasing the transactivation activity of Peroxisome Proliferators Activated Receptors (PPARs). The clinically used TZDs that suffered from several serious side effects and hence withdrawn/updated later, were full agonists of PPAR-γ and potent insulin sensitizers. These drugs were developed at a time when limited data were available on the structure and mechanism of PPARs. In recent years, however, PPAR-α/γ, PPAR-α/δ and PPAR-δ/γ dual agonists, PPAR pan agonists, selective PPAR-γ modulators and partial agonists have been investigated. In addition to these, several non PPAR protein alternatives of TZDs such as FFAR1 agonism, GPR40 agonism and ALR2, PTP1B and α-glucosidase inhibition have been investigated to address the problems associated with the TZDs. Using these rationalized approaches, several investigations have been carried out in recent years to develop newer TZDs devoid of side effects. This report critically reviews TZDs, their history, chemistry, mechanism mediated through PPAR, recent advances and future prospects.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiazolidinediones
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Peroxisome Proliferator-Activated Receptors
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Diabetes Mellitus, Type 2
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Hypoglycemic Agents
Limits:
Animals
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Humans
Language:
En
Journal:
Bioorg Chem
Year:
2018
Document type:
Article
Affiliation country:
India
Publication country:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA