Novel quinolone substituted thiazolidin-4-ones as anti-inflammatory, anticancer agents: Design, synthesis and biological screening

被引：84

作者：

Suthar, Sharad Kumar ^{[1
]}

Jaiswal, Varun ^{[2
]}

Lohan, Sandeep ^{[1
]}

Bansal, Sumit ^{[1
]}

Chaudhary, Anil ^{[3
]}

Tiwari, Amit ^{[3
]}

Alex, Angel Treasa ^{[4
]}

Joesph, Alex ^{[1
]}

机构：

[1] Manipal Coll Pharmaceut Sci, Dept Pharmaceut Chem, Manipal 576104, Karnataka, India

[2] Jaypee Univ Informat Technol, Dept Biotechnol & Bioinformat, Waknaghat 173234, Solan, India

[3] Manipal Coll Pharmaceut Sci, Dept Pharmacol, Manipal 576104, Karnataka, India

[4] Manipal Coll Pharmaceut Sci, Dept Pharmaceut Biotechnol, Manipal 576104, Karnataka, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

Quinolone; Thiazolidin-4-one; NF-kappa B; Docking; Anti-inflammatory; Anticancer; NF-KAPPA-B; DUAL INHIBITORS; IN-VITRO; ACID; DERIVATIVES; DISCOVERY; ALPHA; IDENTIFICATION; ANTIOXIDANT; EXPRESSION;

D O I：

10.1016/j.ejmech.2013.03.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nuclear factor-kappaB (NF-kappa B) has been reported to regulate various genes involved in cancer and inflammation. Accordingly, drugs suppressing or inhibiting NF-kappa B may possess both anti-inflammatory and anticancer properties. A library of quinolone substituted thiazolidin-4-ones was docked into the active site of NF-kappa B and the top-ranked 31 compounds were synthesized and evaluated for anti-inflammatory and anticancer activity. The best-ranked compound 6b showed highest anti-inflammatory activity in carrageenan-induced paw edema model. In vitro anticancer studies revealed la and 16a as most active compounds against BT-549, HeLa, COLO-205 and ACHN human cancer cell lines. Compounds la and 16a exhibited NF-kappa B dependent anticancer properties and apoptosis mediated cell death. In vivo Ehrlich ascites carcinoma study further confirmed the antitumor activity of la and 16a. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：589 / 602

页数：14

共 49 条

[1]

[Anonymous], 2008, OECD Guidelines for the Testing of Chemicals 407, DOI [10.1787/9789264070684-en, DOI 10.1787/9789264070684-EN]

[2] Design, synthesis, and biological evaluation of prazosin-related derivatives as multipotent compounds [J].

Antonello, A ;

Hrelia, P ;

Leonardi, A ;

Marucci, G ;

Rosini, M ;

Tarozzi, A ;

Tumiatti, V ;

Melchiorre, C .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (01) :28-31

[3] Multitarget-directed drug design strategy: A novel molecule designed to block epidermal growth factor receptor (EGFR) and to exert proapoptotic effects [J].

Antonello, Alessandra ;

Tarozzi, Andrea ;

Morroni, Fabiana ;

Cavalli, Andrea ;

Rosini, Michela ;

Hrelia, Patrizia ;

Bolognesi, Maria Laura ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (23) :6642-6645

[4] Development of a novel furocoumarin derivative inhibiting NF-κB dependent biological functions: Design, synthesis and biological effects [J].

Borgatti, Monica ;

Chilin, Adriana ;

Piccagli, Laura ;

Lampronti, Ilaria ;

Bianchi, Nicoletta ;

Mancini, Irene ;

Marzaro, Giovanni ;

dall'Acqua, Francesco ;

Guiotto, Adriano ;

Gambari, Roberto .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (10) :4870-4877

[5] Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells [J].

Charalambous, MP ;

Maihöfner, C ;

Bhambra, U ;

Lightfoot, T ;

Gooderham, NJ .

BRITISH JOURNAL OF CANCER, 2003, 88 (10) :1598-1604

[6]

Contreras J.-M., 2003, The Practice of Medicinal Chemistry, V2nd, P251

[7] Virtual screening with AutoDock: theory and practice [J].

Cosconati, Sandro ;

Forli, Stefano ;

Perryman, Alex L. ;

Harris, Rodney ;

Goodsell, David S. ;

Olson, Arthur J. .

EXPERT OPINION ON DRUG DISCOVERY, 2010, 5 (06) :597-607

[8] Inflammation and cancer [J].

Coussens, LM ;

Werb, Z .

NATURE, 2002, 420 (6917) :860-867

[9] Design and synthesis of novel quinolinone-3-aminoamides and their α-lipoic acid adducts as antioxidant and antiiflammatory agents [J].

Detsi, Anastasia ;

Bouloumbasi, Dionysia ;

Prousis, Kyriakos C. ;

Koufaki, Maria ;

Athanasellis, Giorgos ;

Melagraki, Georgia ;

Afantitis, Antreas ;

Igglessi-Markopoulou, Olga ;

Kontogiorgis, Christos ;

Hadjipavlou-Litina, Dimitra J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (10) :2450-2458

[10] Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents [J].

Esteller, M ;

Garcia-Foncillas, J ;

Andion, E ;

Goodman, SN ;

Hidalgo, OF ;

Vanaclocha, V ;

Baylin, SB ;

Herman, JG .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (19) :1350-1354

← 1 2 3 4 5 →