Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity

被引：84

作者：

Krauth, Fabian ^{[1
]}

Dahse, Hans-Martin ^{[2
]}

Ruettinger, Hans-Hermann ^{[1
]}

Frohberg, Petra ^{[1
]}

机构：

[1] Univ Halle Wittenberg, Inst Pharm, D-06120 Halle, Germany

[2] HKI, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 05期

关键词：

1,2,4-triazin-5-ones; Small molecules; Leukemia; K-562; Rule-of-five; log P; Imatinib; Serum albumin binding; HUMAN SERUM-ALBUMIN; 5-LIPOXYGENASE INHIBITORS; ARYLHYDRAZONIC ACIDS; PROTEIN-BINDING; AGENTS; DRUGS; IDENTIFICATION; ANTIBACTERIAL; AMIDRAZONES; CYCLIZATION;

D O I：

10.1016/j.bmc.2010.01.053

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 novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the 'rule-of-five' claims by Lipinski and calculated log P(calc) values were experimentally confirmed (log P(exp)). For the most active compounds, in vitro serum albumin binding was investigated and structure-activity relationships were established. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1816 / 1821

页数：6

共 29 条

[1]

Abdel-Rahman RM, 2001, PHARMAZIE, V56, P195

[2]

Abdel-Rahman RM, 2001, PHARMAZIE, V56, P18

[3] 5-lipoxygenase inhibitors: Synthesis and structure-activity relationships of a series of 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones [J].

Bhatia, PA ;

Brooks, CDW ;

Basha, A ;

Ratajczyk, JD ;

Gunn, BP ;

Bouska, JB ;

Lanni, C ;

Young, PR ;

Bell, RL ;

Carter, GW .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (20) :3938-3950

[4]

Dahse HM, 2001, PHARMAZIE, V56, P489

[5] Heterocyclic synthesis using nitrilimines. Part 11. Synthesis of 1-aryl-3-phenylaminocarbonyl-4,5-dihydro-1,4,5-triazin-6-ones [J].

Dalloul, Hany M. ;

Mohamed, El-Hossain A. R. ;

Shorafa, Hashem Z. ;

El-Shorafa, Ali Z. .

ARKIVOC, 2008, :207-217

[6] Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide [J].

Damrot, J. ;

Nuebel, T. ;

Epe, B. ;

Roos, W. P. ;

Kaina, B. ;

Fritz, G. .

BRITISH JOURNAL OF PHARMACOLOGY, 2006, 149 (08) :988-997

[7] N-Benzylsalicylthioamides: Highly Active Potential Antituberculotics [J].

Dolezal, Rafael ;

Waisser, Karel ;

Petrlikova, Eva ;

Kunes, Jiri ;

Kubicova, Lenka ;

Machacek, Milos ;

Kaustova, Jarmila ;

Dahse, Hans Martin .

ARCHIV DER PHARMAZIE, 2009, 342 (02) :113-119

[8] Derivatives of arylhydrazonic acids.: Part 2:: A facile approach to novel 4,5-dihydro-1H-1,2,4-triazoles via cyclization of amidrazones [J].

Drutkowski, G ;

Donner, C ;

Schulze, I ;

Frohberg, P .

TETRAHEDRON, 2002, 58 (26) :5317-5326

[9] A GENERAL, WIDE-RANGE SPECTROFLUOROMETRIC METHOD FOR MEASURING THE SITE-SPECIFIC AFFINITIES OF DRUGS TOWARD HUMAN SERUM-ALBUMIN [J].

EPPS, DE ;

RAUB, TJ ;

KEZDY, FJ .

ANALYTICAL BIOCHEMISTRY, 1995, 227 (02) :342-350

[10] Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine [J].

Formariz, T. R. ;

Sarmento, V. H. V. ;

Silva-Junior, A. A. ;

Scarpa, M. V. ;

Santilli, C. V. ;

Oliveira, A. G. .

COLLOIDS AND SURFACES B-BIOINTERFACES, 2006, 51 (01) :54-61

← 1 2 3 →