1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents

被引：53

作者：

Mareddy, Jyoti ^{[1
,2
]}

Suresh, N. ^{[2
]}

Kumar, C. Ganesh ^{[3
]}

Kapavarapu, Ravikumar ^{[4
]}

Jayasree, A. ^{[2
]}

Pal, Sarbani ^{[1
]}

机构：

[1] MNR Degree & PG Coll, Dept Chem, Hyderabad 500085, Andhra Pradesh, India

[2] Jawaharlal Nehru Technol Univ Hyderabad, Inst Sci & Technol, Ctr Chem Sci & Technol, Hyderabad 500085, Andhra Pradesh, India

[3] Indian Inst Chem Technol, Chem Biol Lab, Med Chem & Pharmacol Div, Hyderabad 500007, Andhra Pradesh, India

[4] Univ Coimbra IIIUC, Inst Interdisciplinary Res, Ctr Neurosci & Cell Biol, Doctoral Programme Expt Biol & Biomed, P-3004517 Coimbra, Portugal

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 03期

关键词：

Nimesulide; 1,2,3-Triazole; Azide; Alkyne; Anticancer activity; NIMESULIDE; PHOSPHODIESTERASE; DERIVATIVES; EXPRESSION; INHIBITORS; TRIAZOLE; HEPG2;

D O I：

10.1016/j.bmcl.2016.12.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC50 similar to 6-10 mu M) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60-70% at 10 mu M) that was supported by the docking studies (PLP score 87-94) in silico. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：518 / 523

页数：6

共 41 条

[1]

[Anonymous], CHEM ABSTR, V113, P77922

[2]

[Anonymous], SPRINGERPLUS

[3] Click Chemistry Under Microwave or Ultrasound Irradiation [J].

Barge, Alessandro ;

Tagliapietra, Silvia ;

Binello, Arianna ;

Cravotto, Giancarlo .

CURRENT ORGANIC CHEMISTRY, 2011, 15 (02) :189-203

[4] NIMESULIDE DECREASES SUPEROXIDE PRODUCTION BY INHIBITING PHOSPHODIESTERASE TYPE-IV [J].

BEVILACQUA, M ;

VAGO, T ;

BALDI, G ;

RENESTO, E ;

DALLEGRI, F ;

NORBIATO, G .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1994, 268 (03) :415-423

[5] Mechanisms of NSAID-induced hepatotoxicity - Focus on nimesulide [J].

Boelsterli, UA .

DRUG SAFETY, 2002, 25 (09) :633-648

[6] Structural basis for the activity of drugs that inhibit phosphodiesterases [J].

Card, GL ;

England, BP ;

Suzuki, Y ;

Fong, D ;

Powell, B ;

Lee, B ;

Luu, C ;

Tabrizizad, M ;

Gillette, S ;

Ibrahim, PN ;

Artis, DR ;

Bollag, G ;

Milburn, MV ;

Kim, SH ;

Schlessinger, J ;

Zhang, KYJ .

STRUCTURE, 2004, 12 (12) :2233-2247

[7] MECHANISM OF SELECTIVE-INHIBITION OF THE INDUCIBLE ISOFORM OF PROSTAGLANDIN G/H SYNTHASE [J].

COPELAND, RA ;

WILLIAMS, JM ;

GIANNARAS, J ;

NURNBERG, S ;

COVINGTON, M ;

PINTO, D ;

PICK, S ;

TRZASKOS, JM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (23) :11202-11206

[8] HIGH-LEVEL EXPRESSION OF ACTIVE HUMAN CYCLOOXYGENASE-2 IN INSECT CELLS [J].

CROMLISH, WA ;

PAYETTE, P ;

CULP, SA ;

OUELLET, M ;

PERCIVAL, MD ;

KENNEDY, BP .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1994, 314 (01) :193-199

[9] Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines [J].

Demchuk, Dmitry V. ;

Samet, Alexander V. ;

Chernysheva, Natalia B. ;

Ushkarov, Vladimir I. ;

Stashina, Galina A. ;

Konyushkin, Leonid D. ;

Raihstat, Mikhail M. ;

Firgang, Sergei I. ;

Philchenkov, Alex A. ;

Zavelevich, Michael P. ;

Kuiava, Ludmila M. ;

Chekhun, Vasyl F. ;

Blokhin, Dmitry Yu. ;

Kiselyov, Alex S. ;

Semenova, Marina N. ;

Semenov, Victor V. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (02) :738-755

[10] Enantiodivergent synthesis of (R)- and (S)-rolipram [J].

Demnitz, J ;

LaVecchia, L ;

Bacher, E ;

Keller, TH ;

Muller, T ;

Schurch, F ;

Weber, HP ;

Pombo-Villar, E .

MOLECULES, 1998, 3 (03) :107-119

← 1 2 3 4 5 →