Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: Synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression

被引：45

作者：

Nazreen, Syed ^{[1
]}

Alam, Mohammad Sarwar ^{[1
]}

Hamid, Hinna ^{[1
]}

Yar, Mohammad Shahar ^{[2
]}

Dhulap, Abhijeet ^{[3
]}

Alam, Perwez ^{[4
]}

Pasha, M. A. Q. ^{[4
]}

Bano, Sameena ^{[1
]}

Alam, Mohammad Mahboob ^{[1
]}

Haider, Saqlain ^{[1
,5
]}

Kharbanda, Chetna ^{[1
]}

Ali, Yakub ^{[1
]}

Pillai, K. K. ^{[5
]}

机构：

[1] Jamia Hamdard, Fac Sci, Dept Chem, New Delhi 110062, India

[2] Jamia Hamdard, Fac Pharm, Dept Pharmaceut Chem, New Delhi 110062, India

[3] CSIR, Unit Res & Dev Informat Prod, Pune 411038, Maharashtra, India

[4] CSIR Inst Genom & Integrat Biol, Funct Genom Unit, New Delhi, India

[5] Jamia Hamdard, Fac Pharm, Dept Pharmacol, New Delhi 110062, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 14期

关键词：

2,4-Thiazolidinedione; Chromone; Antidiabetic activity; PPAR-gamma; Hepatotoxicity; ACTIVATED RECEPTOR-GAMMA; DIETARY FLAVONOIDS; HYPOLIPIDEMIC AGENTS; BIOLOGICAL-ACTIVITY; THIAZOLIDINEDIONE; POTENT;

D O I：

10.1016/j.bmcl.2014.05.034

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-gamma transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-gamma target in molecular docking study. PPAR-gamma gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3034 / 3042

页数：9

共 23 条

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Hemlatha, R.
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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (10) : 1801 - 1804
[3] 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. Q.
Bano, Sameena
Alam, Mohammad Mahboob
Haider, Saglain
Ali, Yakub
Kharbanda, Chetna
Pillai, K. K.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 87 : 175 - 185
[4] Design, Synthesis, and Biological Evaluation of Thiazolidine-2,4-dione Conjugates as PPAR- Agonists
Nazreen, Syed
Alam, Mohammad Sarwar
Hamid, Hinna
Yar, Mohammad Shahar
Dhulap, Abhijeet
Alam, Perwez
Pasha, Mohammad Abdul Qadar
Bano, Sameena
Alam, Mohammad Mahboob
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Kharbanda, Chetna
Ali, Yakub
Pillai, Kolakappi
ARCHIV DER PHARMAZIE, 2015, 348 (06) : 421 - 432
[5] Development of novel thiazolidine-2,4-dione derivatives as PPAR-γ agonists through design, synthesis, computational docking, MD simulation, and comprehensive in vitro and in vivo evaluation
Srinivasa, Mahendra Gowdru
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RSC MEDICINAL CHEMISTRY, 2023, 14 (11): : 2401 - 2416
[6] Rational design and synthesis of some PPAR-γ agonists: Substituted benzylideneamino-benzylidene-thiazolidine-2,4-diones
Chhajed, Santosh S.
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Kshirsagar, Sanjay K.
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[7] 5-aryl thiazolidine-2,4-diones:: Discovery of PPAR dual α/γ agonists as antidiabetic agents
Desai, RC
Han, W
Metzger, EJ
Bergman, JP
Gratale, DF
MacNaul, KL
Berger, JP
Doebber, TW
Leung, K
Moller, DE
Heck, JV
Sahoo, SP
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (16) : 2795 - 2798
[8] SYNTHESIS, IN VITRO ANTIOXIDANT AND ANTIDIABETIC ACTIVITY EVALUATION OF NOVEL THIAZOLIDINE-2,4-DIONES
Swathi, N.
Himabindu, N.
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INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY, 2014, 24 (02) : 145 - 152
[9] Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists
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Scientific Reports, 13
[10] Synthesis, molecular docking, and in vivo antidiabetic evaluation of new benzylidene-2,4-thiazolidinediones as partial PPAR-γ agonists
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SCIENTIFIC REPORTS, 2023, 13 (01)

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