Synthesis and Biological Evaluation of Salicylic Acid Analogues of Celecoxib as a New Class of Selective Cyclooxygenase-1 Inhibitor

被引：9

作者：

Yoon, Sung-Hwa ^{[1
]}

Cho, Duk-Yeon ^{[2
]}

Choi, Seoung-Ryoung ^{[3
]}

Lee, Joo-Young ^{[1
]}

Choi, Dong-Kug ^{[2
]}

Kim, Eunha ^{[1
]}

Park, Ju-Young ^{[4
]}

机构：

[1] Ajou Univ, Dept Mol Sci & Technol, 206 Worldcup Ro, Suwon 16499, South Korea

[2] Konkuk Univ, Dept Appl Life Sci & Integrated Biosci, 268 Chungwon Daero, Chungju 27478, South Korea

[3] Univ Nebraska Med Ctr, Coll Med, Dept Pathol & Microbiol, 42nd & Emile, Omaha, NE 68198 USA

[4] Ajou Univ, Mol Sci & Technol Res Ctr, 206 Worldcup Ro, Suwon 16499, South Korea

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2021年 / 44卷 / 09期

基金：

新加坡国家研究基金会;

关键词：

celecoxib salicylic acid analogue; selective cyclooxygenase-1 inhibitor; docking; COX-1; INHIBITORS; DESIGN; IDENTIFICATION; DERIVATIVES; SULFONAMIDE; EXPRESSION; SYNTHASE;

D O I：

10.1248/bpb.b20-00991

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A series of salicylic acid analogues of celecoxib where the phenylsulfonamide moiety in the structure of celecoxib is replaced by salicylic acid moiety was synthesized and tested for in vitro cyclooxygenase (COX)-1 and COX-2 enzyme inhibition. Among the series, 5-substituted-2-hydroxy-benzoic acid analogues (7a-7h) generally showed better inhibitory activities on both enzymes than 4-substituted-2-hydroxy-benzoic acid analogues (12a-12h). In particular, the chloro analogue 7f which had the highest inhibitory effect (IC50 = 0.0057 mu M) to COX-1 with excellent COX-1 selectivity (SI = 768) can be classified as a new potent and selective COX-1 inhibitor. The high inhibitory potency of 7f was rationalized through the docking simulation of this analogue in the active site of COX-1 enzyme.

引用

页码：1230 / 1238

页数：9

共 37 条

[1] Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile [J].

Abdelazeem, Ahmed H. ;

El-Saadi, Mohammed T. ;

El-Din, Asmaa G. Safi ;

Omar, Hany A. ;

El-Moghazy, Samir M. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (02) :665-676

[2] Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,5-diarylpyrazole derivatives [J].

Abdellatif, Khaled R. A. ;

Fadaly, Wael A. A. ;

Ali, Waleed A. M. ;

Kamel, Gehan M. .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2016, 31 :54-60

[3] CYP2C9 structure-metabolism relationships:: Optimizing the metabolic stability of COX-2 inhibitors [J].

Ahlstroem, Marie M. ;

Ridderstroem, Marianne ;

Zamora, Ismael ;

Luthman, Kristina .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (18) :4444-4452

[4] Synthesis and biological evaluation of pyridazinone derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents [J].

Ahmed, Eman M. ;

Kassab, Asmaa E. ;

El-Malah, Afaf A. ;

Hassan, Marwa S. A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 171 :25-37

[5] Discovery of potential and selective COX-1 inhibitory leads using pharmacophore modelling, in silico screening and in vitro evaluation [J].

Balaji, Bhaskar ;

Hariharan, Sivaram ;

Shah, Darshit B. ;

Ramanathan, Muthiah .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 86 :469-480

[6] Structural and functional basis of cyclooxygenase inhibition [J].

Blobaum, Anna L. ;

Marnett, Lawrence J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (07) :1425-1441

[7] Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells [J].

Bottone, FG ;

Martinez, JM ;

Alston-Mills, B ;

Eling, TE .

CARCINOGENESIS, 2004, 25 (03) :349-357

[8] Novel selective COX-1 inhibitors suppress neuroinflammatory mediators in LPS-stimulated N13 microglial cells [J].

Calvello, Rosa ;

Panaro, Maria Antonietta ;

Carbone, Maria Luigia ;

Cianciulli, Antonia ;

Perrone, Maria Grazia ;

Vitale, Paola ;

Malerba, Paola ;

Scilimati, Antonio .

PHARMACOLOGICAL RESEARCH, 2012, 65 (01) :137-148

[9] Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors [J].

Chandna, Nisha ;

Kumar, Satish ;

Kaushik, Pawan ;

Kaushik, Dhirender ;

Roy, Somendu K. ;

Gupta, Girish K. ;

Jachak, Sanjay M. ;

Kapoor, Jitander K. ;

Sharma, Pawan K. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (15) :4581-4590

[10] Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors [J].

Chen, Zhong ;

Wang, Zhong-Chang ;

Yan, Xiao-Qiang ;

Wang, Peng-Fei ;

Lu, Xiao-Yuan ;

Chen, Long-Wang ;

Zhu, Hai-Liang ;

Zhang, Hong-Wei .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (09) :1947-1951

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