Synthesis, cytotoxic activity, and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones

被引：30

作者：

Abbas, Samar Hafez ^{[1
]}

Abuo-Rahma, Gamal El-Din A. A. ^{[1
]}

Abdel-Aziz, Mohamed ^{[1
]}

Aly, Omar M. ^{[1
]}

Beshr, Eman A. ^{[1
,2
]}

Gamal-Eldeen, Amira M. ^{[3
]}

机构：

[1] Menia Univ, Fac Pharm, Dept Med Chem, Al Minya 61519, Egypt

[2] Umm Al Qura Univ, Coll Pharm, Dept Pharmaceut Chem, Mecca 21955, Saudi Arabia

[3] Natl Res Ctr, Ctr Excellence Adv Sci, Canc Biol Lab, Giza, Egypt

来源：

BIOORGANIC CHEMISTRY | 2016年 / 66卷

关键词：

Pyrrolone; Pyridazinone; Cytotoxicity; Tubulin; Immunofluorescence; Docking study; COMBRETASTATIN A-4 ANALOGS; BIOLOGICAL EVALUATION; 2(3H)-FURANONES; DERIVATIVES; 2(3H)-PYRROLONES; BINDING; DESIGN; ACIDS;

D O I：

10.1016/j.bioorg.2016.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of new pyrrol-2(3H)-ones 4a-f and pyridazin-3(2H)-ones 7a-f were synthesized and characterized using different spectroscopic tools. Some of the tested compounds revealed moderate activity against 60 cell lines. The E form of the pyrrolones 4 showed good cytotoxic activity than both the Z form and the corresponding open amide form. Furthermore, the in vitro cytotoxic activity against HepG2 and MCF-7 cell lines revealed that compounds (E) 4b, 6f and 7f showed good cytotoxic activity against HepG2 with IC50 values of 11.47, 7.11 and 14.80 mu M, respectively. Compounds (E) 4b, 6f, 7d and 7f showed a pronounced inhibitory effect against cellular localization of tubulin. Flow cytometric analysis indicated that HepG2 cells treated with (E) 4b showed a predominated growth arrest at the S-phase compared to that of G2/M-phase. Molecular modeling study using MOE (R) program indicated that most of the target compounds showed good binding of beta-subunit of tubulin with the binding free energy (dG) values about -10 kcal/mole. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：46 / 62

页数：17

共 43 条

[1]

Abolhasani H, 2015, IRAN J PHARM RES, V14, P141

[2] Synthesis and pharmacological evaluation of 2(3H)-furanones and 2(3H)-pyrrolones, combining analgesic and anti-inflammatory properties with reduced gastrointestinal toxicity and lipid peroxidation [J].

Alam, M. M. ;

Husain, Asif ;

Hasan, S. M. ;

Suruchi ;

Anwer, T. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2009, 44 (06) :2636-2642

[3] Synthesis of quinoline-attached furan-2(3H)-ones having anti-inflammatory and antibacterial properties with reduced gastro-intestinal toxicity and lipid peroxidation [J].

Alam, Mohammad M. ;

Sarkar, Deba Priya ;

Husain, Asif ;

Marella, Akranth ;

Shaquiquzzaman, Mohammad ;

Akhter, Mymoona ;

Shaharyar, Mohammad ;

Alam, Ozair ;

Azam, Faizul .

JOURNAL OF THE SERBIAN CHEMICAL SOCIETY, 2011, 76 (12) :1617-1626

[4] SIR92 - a program for automatic solution of crystal structures by direct methods [J].

ALTOMARE, A ;

CASCARANO, G ;

GIACOVAZZO, G ;

GUAGLIARDI, A ;

BURLA, MC ;

POLIDORI, G ;

CAMALLI, M .

JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1994, 27 :435-435

[5]

[Anonymous], 1987, INDIAN J CHEM B, V26, P427

[6]

Asif M., 2010, CHRON YOUNG SCI, V1, P3, DOI [DOI 10.4103/4444-4443.76447, 10.4103/4444-4443.76447]

[7] Synthesis and biological activity of vicinal diaryl-substituted 1H-imidazoles [J].

Bellina, Fabio ;

Cauteruccio, Silvia ;

Rossi, Renzo .

TETRAHEDRON, 2007, 63 (22) :4571-4624

[8] Novel imidazole-based combretastatin A-4 analogues: Evaluation of their in vitro antitumor activity and molecular modeling study of their binding to the colchicine site of tubulin [J].

Bellina, Fabio ;

Cauteruccio, Silvia ;

Monti, Susanna ;

Rossi, Renzo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (22) :5757-5762

[9] Synthesis and in vitro cytotoxicity of andrographolide-19-oic acid analogues as anti-cancer agents [J].

Chen, Dongsheng ;

Song, Yaping ;

Lu, Yunlong ;

Xue, Xiaowen .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (11) :3166-3169

[10]

Deo S, 2010, ASIAN J CHEM, V22, P3362

← 1 2 3 4 5 →