Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity

被引：28

作者：

Di Capua, Angela ^{[1
,8
]}

Sticozzi, Claudia ^{[2
]}

Brogi, Simone ^{[1
]}

Brindisi, Margherita ^{[1
]}

Cappelli, Andrea ^{[1
]}

Sautebin, Lidia ^{[3
]}

Rossi, Antonietta ^{[3
]}

Pace, Simona ^{[3
]}

Ghelardini, Carla ^{[4
]}

Mannelli, Lorenzo Di Cesare ^{[4
]}

Valacchi, Giuseppe ^{[2
,5
]}

Giorgi, Gianluca ^{[1
]}

Giordani, Antonio ^{[6
]}

Poce, Giovanna ^{[7
]}

Biava, Mariangela ^{[7
]}

Anzini, Maurizio ^{[1
]}

机构：

[1] Univ Siena, Dept Biotechnol Chem & Pharm, Via Aldo Moro 2, I-53100 Siena, Italy

[2] Univ Ferrara, Dept Life Sci & Biotechnol, Via Luigi Borsari 46, I-44121 Ferrara, Italy

[3] Univ Naples Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy

[4] Univ Florence, Dept Pharmacol Neurosci Psychol Drug Res & Child, Pharmacol & Toxicol Sect, Viale G Pieraccini 6, I-50139 Florence, Italy

[5] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea

[6] Rottapharm Biotech, Via Valosa di Sopra 7, I-20052 Monza, Italy

[7] Univ Roma La Sapienza, Dept Chem Studies & Technol Drugs, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[8] Griffith Univ, Eskitis Inst Drug Discovery, Brisbane, Qld 4111, Australia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 109卷

关键词：

COX-2; inhibitors; 1,5-diarylpyrrole derivatives; Anti-inflammatory agents; Antinociceptive agents; Antiproliferative activity; Molecular modelling; INDUCED EXPERIMENTAL OSTEOARTHRITIS; NITRIC-OXIDE DONORS; CYCLOOXYGENASE-2; INHIBITORS; ACCURATE DOCKING; FORCE-FIELD; CANCER; DRUGS; AGENTS; PAIN; RAT;

D O I：

10.1016/j.ejmech.2015.12.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers were previously synthesized and the potential anti-inflammatory and antinociceptive activities of these compounds were evaluated in vivo. The compounds displayed a very good activity against both carrageenan-induced hyperalgesia and oedema in the rat paw test. Therefore, in a very preliminary test, compounds (8a,b) showed antiproliferative activity in the HaCaT (aneuploid immortal keratinocyte from adult human skin) cell models. On these basis, our research continued with the synthesis of fluorinated derivatives (8c,d, 9b-d, and 10b-d) with the aim of improving the pharmacokinetic profile of the previous active compounds. Substitution of a hydrogen atom by a fluorine atom may change the conformational preferences of the molecules due to stereo electronic effects and also fluorine atom may be able to exert the metabolic obstruction reducing the "first-pass effect'. Compound 10b exhibited a prominent in vivo anti-inflammatory and antinociceptive activities, in addition its antiproliferative power in an in vitro model of human skin cancer is herein described. (C) 2015 Elsevier Masson SAS. All rights reserved.

引用

页码：99 / 106

页数：8

共 50 条

[41] Synthesis, biological evaluation, docking study and ulcerogenicity profiling of some novel quinoline-2-carboxamides as dual COXs/LOX inhibitors endowed with anti-inflammatory activity [J].

Abdelrahman, Mostafa H. ;

Youssif, Bahaa G. M. ;

Abdelgawad, Mohamed A. ;

Abdelazeem, Ahmed H. ;

Ibrahim, Hussein M. ;

Moustafa, Abd El Ghany A. ;

Treamblu, Laurent ;

Bukhari, Syed Nasir Abbas .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 127 :972-985

[42] Synthesis, biological evaluation and docking study of a new series of di-substituted benzoxazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents [J].

Kaur, Avneet ;

Pathak, Dharam P. ;

Sharma, Vidushi ;

Wakode, Sharad .

BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (04) :891-902

[43] Synthesis, anti-inflammatory activity and COX-1/COX-2 inhibition of novel substituted cyclic imides. Part 1: Molecular docking study [J].

Abdel-Aziz, Alaa A-M. ;

ElTahir, Kamal E. H. ;

Asiri, Yousif A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (05) :1648-1655

[44] Synthesis and Biological Evaluation of New imidazo[1,2-a]pyridine Derivatives as Selective COX-2 Inhibitors [J].

Movahed, Mahsa Azami ;

Daraei, Bahram ;

Zarghi, Afshin .

LETTERS IN DRUG DESIGN & DISCOVERY, 2016, 13 (08) :793-799

[45] Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies [J].

Abdelgawad, Mohamed A. ;

Labib, Madlen B. ;

Ali, Waleed A. M. ;

Kamel, Gehan ;

Azouz, Amany A. ;

El-Nahass, EL-Shaymaa .

BIOORGANIC CHEMISTRY, 2018, 78 :103-114

[46] 2,5-Diaryl-1,3,4-oxadiazoles as selective COX-2 inhibitors and anti-inflammatory agents [J].

Grover, Jagdeep ;

Bhatt, Nirav ;

Kumar, Vivek ;

Patel, Neeraj K. ;

Gondaliya, Bhagirath J. ;

Sobhia, M. Elizabeth ;

Bhutani, Kamlesh K. ;

Jachak, Sanjay M. .

RSC ADVANCES, 2015, 5 (56) :45535-45544

[47] N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: Synthesis and biological evaluation [J].

Kaur, Jatinder ;

Bhardwaj, Atul ;

Huang, Zhangjian ;

Knaus, Edward E. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (06) :2154-2159

[48] 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

[49] Potential COX-2 inhibitors modulating NF-κB/MAPK signaling pathways: Design, synthesis and evaluation of anti-inflammatory activity of Pterostilbene-carboxylic acid derivatives with an oxime ether moiety [J].

Luo, Peng ;

Chen, Taotao ;

Huang, Shaoling ;

Peng, Feng ;

Huang, Yunhou ;

Pan, Weigao .

BIOORGANIC & MEDICINAL CHEMISTRY, 2025, 118

[50] 1,2,3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity [J].

Naaz, Fatima ;

Pallavi, M. C. Preeti ;

Shafi, Syed ;

Mulakayala, Naveen ;

Yar, M. Shahar ;

Kumar, H. M. Sampath .

BIOORGANIC CHEMISTRY, 2018, 81 :1-20

← 1 2 3 4 5 →