Thieno[2,3-b]pyridines-A new class of multidrug resistance (MDR) modulators

被引：37

作者：

Krauze, Aivars ^{[1
]}

Grinberga, Signe ^{[1
]}

Krasnova, Laura ^{[1
]}

Adlere, Ilze ^{[1
]}

Sokolova, Elina ^{[1
]}

Domracheva, Ilona ^{[1
]}

Shestakova, Irina ^{[1
]}

Andzans, Zigmars ^{[1
]}

Duburs, Gunars ^{[1
]}

机构：

[1] Latvian Inst Organ Synth, LV-1006 Riga, Latvia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 21期

关键词：

Thieno[2,3-b]pyridine; Multidrug resistance modulators; P-glycoprotein; Multidrug resistance-associated protein; Breast cancer resistance protein; P-GLYCOPROTEIN; DERIVATIVES; INHIBITORS; THIENOPYRIDINE; AGENTS; REVERSAL; PROTEIN; DESIGN; BCRP; ABC;

D O I：

10.1016/j.bmc.2014.09.023

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：

To identify new potent multidrug resistance modulators, we have synthesized a series of novel thieno[ 2,3-b]pyridines and furo[2,3-b] pyridines, and examined their stucture-activity relationships. All synthesized compounds were tested to determine BCRP1, P-gp, and MRP1 inhibitor activity, and most potent MDR modulators were also screened for their toxicity, cytotoxicity and Ca2+ channel antagonist activity. Among these compounds, thieno[2,3-b] pyridine (6r) was found to exhibit a potent P-gp inhibitory action with EC50 = 0.3 +/- 0.2 mu M, MRP1 inhibitory action with EC50 = 1.1 +/- 0.1 mu M and BCRP1 inhibitory action with EC50 = 0.2 +/- 0.05 mu M and may represent suitable candidate for further pharmacological studies. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5860 / 5870

页数：11

共 44 条

[1] Cyanothioacetamide and Its Derivatives in Heterocyclic Chemistry: Synthesis of Some New Thioxopyridine, Thienopyridine, and Pyridothienopyrimidine Derivatives
Abunada, Nada M.
El-Louh, Ali K. K.
Al-Zaeem, Ismaeel S.
[J]. PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 2009, 184 (03) : 591 - 601
[2] [Anonymous], 1992, INVITTOX PROTOCOL 64
[3] [Anonymous], 1999, GRAPHPAD PRISM SOFTW
[4] Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography
Bauer, Florian
Wanek, Thomas
Mairinger, Severin
Stanek, Johann
Sauberer, Michael
Kuntner, Claudia
Parveen, Zahida
Chiba, Peter
Mueller, Markus
Langer, Oliver
Erker, Thomas
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2012, 696 (1-3) : 18 - 27
[5] Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor
Bauer, Florian
Kuntner, Claudia
Bankstahl, Jens P.
Wanek, Thomas
Bankstahl, Marion
Stanek, Johann
Mairinger, Severin
Doerner, Bernd
Loescher, Wolfgang
Mueller, Markus
Erker, Thomas
Langer, Oliver
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (15) : 5489 - 5497
[6] Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties
Baumert, Christiane
Guenthel, Marianne
Krawczyk, Soeren
Hemmer, Marc
Wersig, Tom
Langner, Andreas
Molnar, Josef
Lage, Hermann
Hilgeroth, Andreas
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (01) : 166 - 177
[7] Recent Advances in the Development of P-gp Inhibitors
Baumert, Christiane
Hilgeroth, Andreas
[J]. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2009, 9 (04) : 415 - 436
[8] Brangi M, 1999, CANCER RES, V59, P5938
[9] Brooking D. C., 2009, WO Patent, Patent No. [2009/093008 A1, 2009093008]
[10] Computational models for predicting substrates or inhibitors of P-glycoprotein
Chen, Lei
Li, Youyong
Zhang, Huidong
Zhang, Liling
Hou, Tingjun
[J]. DRUG DISCOVERY TODAY, 2012, 17 (7-8) : 343 - 351

← 1 2 3 4 5 →