Thiazolidine-2,4-dione (TZD) is one of the most frequently encountered heterocyclic rings
which has been implicated in design and synthesis of entities for various pathogenic conditions including
cancer. Since its discovery various substitutions at 5th position have been carried out and reviewed.
Various substitutions at 5th position have led to generation of glitazones, whose target peroxisome
proliferating activated receptor γ (PPARγ) was found decade after their discovery. Acidic hydrogen
(-NH) of TZD is a prime pharmacophoric requirement for the activation of PPARγ. However, advanced
in-silico techniques have helped to design compounds bearing substitutions at both methylene
and –NH group of TZD, targeting range of enzymes involved in various pathological conditions viz.,
diabetes, hyperlipidemia, infectious disease, inflammation and cancer. The promising activities shown
by methylene and N-substituted TZDs in above mentioned therapeutic areas, prompted us to collate
the information which would help researchers to alter the structure of existing ligands and to design
new TZD derivatives with better safety and efficacy profiles.