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 11 条

[1] 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
[2] 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
Haider, Saqlain
Kharbanda, Chetna
Ali, Yakub
Pillai, Kolakappi
ARCHIV DER PHARMAZIE, 2015, 348 (06) : 421 - 432
[3] 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
Revanasiddappa, B. C.
Prabhu, Ashwini
Rani, Vinitha
Ghate, Sudeep D.
Kumar, B. R. Prashantha
RSC MEDICINAL CHEMISTRY, 2023, 14 (11): : 2401 - 2416
[4] Rational design and synthesis of some PPAR-γ agonists: Substituted benzylideneamino-benzylidene-thiazolidine-2,4-diones
Chhajed, Santosh S.
Chaskar, Shital
Kshirsagar, Sanjay K.
Haldar, G. M. Animeshchandra
Mahapatra, Debarshi Kar
COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2017, 67 : 260 - 265
[5] SYNTHESIS, IN VITRO ANTIOXIDANT AND ANTIDIABETIC ACTIVITY EVALUATION OF NOVEL THIAZOLIDINE-2,4-DIONES
Swathi, N.
Himabindu, N.
Subrahmanyam, C. V. S.
Satyanarayana, K.
INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY, 2014, 24 (02) : 145 - 152
[6] Synthesis, docking, in vitro and in vivo antidiabetic activity of pyrazole-based 2,4-thiazolidinedione derivatives as PPAR- modulators
Naim, Mohd Javed
Alam, Ozair
Alam, Md Jahangir
Shaquiquzzaman, Mohammad
Alam, Md Mumtaz
Naidu, Vegi Ganga Modi
ARCHIV DER PHARMAZIE, 2018, 351 (3-4)
[7] Conformational Analysis and Docking Study of PPAR-γ Agonists Having Substituted Pyrrolidine Containing Thiazolidine-2,4-Dione Moiety
Sonawane, Lalit V.
Poul, Bhagwat N.
Bari, Sanjaykumar B.
LATIN AMERICAN JOURNAL OF PHARMACY, 2014, 33 (09): : 1413 - 1417
[8] Design, synthesis, and antidiabetic evaluation of thiazolidinedione derivatives as potent PPAR-γ Agonists: Insights from molecular docking, MD simulations and invitro studies
Srinivasa, Mahendra Gowdru
Pujar, Karthik G.
Prabhakaran, Prabitha
JOURNAL OF MOLECULAR STRUCTURE, 2025, 1328
[9] Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists
Abdelgawad, Mohamed A.
El-Adl, Khaled
El-Hddad, Sanadelaslam S. A.
Elhady, Mostafa M.
Saleh, Nashwa M.
Khalifa, Mohamed M.
Khedr, Fathalla
Alswah, Mohamed
Nayl, AbdElAziz A.
Ghoneim, Mohammed M.
Abd El-Sattar, Nour E. A.
PHARMACEUTICALS, 2022, 15 (02)
[10] Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists
Darwish, Khaled M.
Salama, Ismail
Mostafa, Samia
Gomaa, Mohamed S.
Khafagy, El-Sayed
Helal, Mohamed A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (09) : 1595 - 1602

← 1 2 →