Ever since the synthesis of thiazolidinedione (TZD) (1) at
around the turn of the 20th century1, the chemistry of this class of compounds
and their derivatives has been an interesting area of research because of their
broad spectrum of biological activities.
In line to that, two compounds viz. Pioglitazone (2) and Rosiglitazone
(3) were approved by FDA for the treatment of type 2 diabetes2,3. In 1956,
Brown et al1 discovered a series of alkylidine TZDs (XXX) with good antifungal
activity against Aspergillus niger growth.
Some other biological activities associated with thiazolidinediones
reported so far are briefly described here.
Datar et al4 synthesized a new series of thiazolidinedione
derivatives carrying carboxylic acid moiety (1) and evaluated for their
antidiabetic activity. Compounds 1a and
1b exhibited prominent hypoglycemic activities at 100 mg/kg comparable to that
of standard drug Pioglitazone. R=OCH3, R1=H (a); R=OCH3, R1=OCH3 (b), R=OH,
R1=H (c), R=OH, R1=OCH3 (d).
A new series of nitrofurylidene thiazolidinedione (2) was
reported by Mallick et al5. These compounds were screened for their in vitro
antimicrobial activities. Some of tested compounds showed good antibacterial,
antifungal and antiprotozoal activities comparable to those of standard drugs
Benzylpenicillin, Emphotericin B and Metronidazole respectively. n=0,1; R=H,
NO2; R1=H, CH3, p-ClC6H4CH2, CH2CO2C2H5, C6H5CH2.
Ashok at al6 reported
the synthesis of new series of benzylidene thiazolidionedione bearing
oxadiazole moiety (3) as possible anticancer agents. These compounds were
synthesized by refluxing a mixture of pre-synthesized acid hydrazide (X) with
substituted aromatic acids in POCl3 R= H, OCH3; R1= H, OCH3, NO2, OH, Br, Cl,
F; R3= H, OCH3, NO2.
Synthesis, antioxidant and xanthine oxidase inhibitory
activities of a series of new thiazolidinedione derivatives were reported by
Begum et al7. Compounds 4a, 4e and 4d
showed potent DPPH radical scavenger activity with the same magnitude as
standard BHA. Compounds 4c, 4h and 4i exhibited good Xanthine oxidase
inhibitory activity comparable to that of standard drug Allopurinol. R= nC7H15
(a), -(CH2)3CHBrCH3 (b), nC6H13 (c), nC9H19 (d), -(CH2)8Br (e), -(CH2)3COOC2H5
(f), -CH2COOC2H5 (g), -(CH2)6CN (h).
Azizmohammadi et al8 synthesized a new series of
N-substituted thiazolidinedione derivatives (5) as possible anticancer agents.
These compounds were prepared by Knoevenagel condensation of
chromene-3-carbaldehydes (X) with thiazolidinediones (XX) in methanol solvent
and using piperidine as catalyst. R=H, 6-Br, 8-OCH3; R1=H, CH3; R2=H, CH3,
Barros et al9 reported a series of arylidene
thiazolidinedione derivatives (6) having good anti-inflammatory activity
R=2-Br, 3-Cl, 2-Cl-6-F; Ar=5-Br-2-OCH3C6H3, 4-SO2CH3C6H4, 4-C6H5C6H4,
3-Br-4-OCH3C6H3, 4-OCH3C6H4, 2,4-Cl2C6H3.
Bozdag?-Dundar et al10 synthesized a new series of
thiazolidinedione derivatives bearing thiazole moiety (7) and evaluated for
their antimicrobial activity. All tested compounds showed promising antibacterial
and antifungal properties R=H, Cl; R1=H, F, Cl, Br, NO2. Synthesis and
antidiabetic activity of new thiazolidinedione derivatives (8) were reported by
Gupta et al11. Biological study results showed that most of them are good
euglycemic and hypolipidemic agents n=2,3; R=H, CH3, C6H5.
A series of thiazolidinedione derivatives (9) were
synthesized by Sharma et al12 and evaluated for their in vitro antimalarial
activity against FP-2 and the chloroquine resistant W2 strain of P. falciparum.
Compounds 9a and 9b exhibited potent antimalarial activity in the series
R=2-Cl (a), 4-Cl (b).
Barreto de Melo Rego et al13 reported the synthesis, in
vitro and in silico anticancer activities of new disubstituted
thiazolidinedione derivatives (10). These compounds were prepared by the
condensation of various thiazolidinediones (X) and substituted
ethyl-2-cyano-3-phenylacrylate (X) in ethanol containing catalytic amount of
piperidine R=3-Br, 3-Br-4-OCH3, 3,4,5-(OCH3)3. Verma et al14 reported the
synthesis and docking studies of thiazolidinedione derivatives (11) as
inhibitors of protein tyrosine phosphatase (PTP-1B). Compounds 11a showed the
lowest IC50= 0.24 µM than standard drugs Pioglitazone (IC50=220 µM),
Rosiglitazone (IC50 =400 µM), hence acts as promising antidiabetic agent for
the management of type-2 diabetes mellitus.
(12) as possible anti-in?ammatory agents and inhibitors of autoimmune diseases
such as Rheumatoid Arthritis was reported by Junior et al15.
Berczy?ski et al16 synthesized a new series of
thiazolidinedione derivatives (13) bearing chromone moiety and evaluated for
their antioxidant activity. These compounds were synthesized by the Knoevenagel
reaction between the chromone-3-carboxaldehyde with substituted
thiazolidinediones. Compounds 13c and 13d were found to be potent antioxidant
agents by various in vitro methods such as chemiluminescence, EPR spectroscopy
and EPR spin trapping methods as well as Hydroxyl Radical and DPPH radical
scavenging assay R=H (a), 4-F (b), 4-Cl (c), 4-Br (d), 2,4-Cl2 (e), 4-NO2