Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists

Nazreen, Syed; Alam, Mohammad Sarwar; Hamid, Hinna; Yar, Mohammad Shahar; Shafi, Syed; Dhulap, Abhijeet; Alam, Perwez; Pasha, M. A. Qadar; Bano, Sameena; Haider, Saqlain; Ali, Yakub; Kharbanda, Chetna; Pillai, K. K.

doi:10.1016/j.ejmech.2014.09.010

Cited by 70 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The blood glucose level of each group was checked at 0, 1, 7, and 15 days through glucose oxidase method. The experiments performed followed the rules of Institutional Animals Ethics Committee (registration number 173‐CPCSEA) …”

Section: Methodsmentioning

confidence: 99%

Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole‐based 2,4‐thiazolidinedione derivatives as PPAR‐γ modulators

Naim

Alam

et al. 2018

Archiv der Pharmazie

View full text Add to dashboard Cite

The design, synthesis, structure-activity relationship, and biological activity of 2,4-thiazolidinedione derivatives as peroxisome proliferator-activated receptor-γ (PPAR-γ) modulators for antidiabetic activity are reported. Fifteen 2,4-thiazolidinedione derivatives clubbed with pyrazole moiety were docked into the ligand binding domain of PPAR-γ by the Glide XP module of Schrodinger. Eight derivatives (5a, 5b, 5d, 5f, 5i, 5l, 5n, 5o) having Glide XP scores > -8 as compared to the standard drug, rosiglitazone (Glide XP score = -9.165), showed almost similar interaction with the amino acids such as HIS 449, TYR 473, TYR 327, HIS 323, and SER 289 in the molecular docking studies. These eight derivatives were further screened for PPAR-γ transactivation and in vivo blood glucose lowering activity in the streptozotocin-induced diabetic rat model. Compounds 5o, 5n, 5a, 5i, and 5b showed 52.06, 51.30, 48.65, 43.13, and 40.36% PPAR-γ transactivation as compared to the reference drugs rosiglitazone and pioglitazone with 85.30 and 65.22% transactivation, respectively. The data analysis showed significant blood glucose lowering effects (hypoglycemia) of compounds 5o, 5n, and 5a (140.1 ± 4.36, 141.4 ± 6.15, and 150.7 ± 4.15, respectively), along with reference drugs pioglitazone (135.2 ± 4.91) and rosiglitazone (141.1 ± 5.88) as compared to the diabetic control. Furthermore, the most potent compound 5o also elevated the PPAR-γ gene expression by 2.35-fold as compared to rosiglitazone (1.27-fold) and pioglitazone (1.6-fold). It also significantly lowered the AST, ALT, and ALP levels and caused no damage to the liver.

show abstract

Section: Methodsmentioning

confidence: 99%

Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole‐based 2,4‐thiazolidinedione derivatives as PPAR‐γ modulators

Naim

Alam

et al. 2018

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…The antidiabetic activity was performed according to the reported method using STZ‐induced diabetic model. Albino Wistar rats of either sex, 150–200 g, were obtained from Central Animal House, Jamia Hamdard University, New Delhi.…”

Section: Methodsmentioning

confidence: 99%

“…PCR was performed in triplicate and was repeated two times for each gene and each sample. Relative transcript quantities were calculated using the Ct method with β‐actin as the endogenous reference gene . The results are summarized in Fig.…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Thiazolidine‐2,4‐dione Conjugates as PPAR‐γ Agonists

Nazreen

Alam

Hamid

et al. 2015

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione 5a-m showed potent peroxisome proliferator activated receptor-γ (PPAR-γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds 5l and 5m exhibited PPAR-γ transactivation of 54.21 and 55.41%, respectively, in comparison to the standard drugs pioglitazone and rosiglitazone, which showed 65.94 and 82.21% activation, respectively. Compounds 5l and 5m significantly lowered the blood glucose level of STZ-induced diabetic rats. Compounds 5l and 5m lowered the AST, ALT, and ALP levels more than the standard drug pioglitazone. PPAR-γ gene expression was significantly increased by compound 5m (2.00-fold) in comparison to the standard drugs pioglitazone (1.5-fold) and rosiglitazone (1.0-fold). Compounds 5l and 5m did not cause any damage to the liver and could be considered as promising candidates for the development of new antidiabetic agents.

show abstract

“…Two of the compounds may be considered as potential candidates for development of new antidiabetic agents [18].…”

Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online Volume 17, Issue 1, January 2015

Terrett¹

2015

Combinatorial Chemistry - an Online Journal

View full text Add to dashboard Cite

Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists

Cited by 70 publications

References 32 publications

Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole‐based 2,4‐thiazolidinedione derivatives as PPAR‐γ modulators

Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole‐based 2,4‐thiazolidinedione derivatives as PPAR‐γ modulators

Design, Synthesis, and Biological Evaluation of Thiazolidine‐2,4‐dione Conjugates as PPAR‐γ Agonists

Combinatorial Chemistry Online Volume 17, Issue 1, January 2015

Contact Info

Product

Resources

About