MTD-CoMSIA modelling of HMG-CoA reductase inhibitors

被引：4

作者：

Duda-Seiman, Daniel M. ^{[5
]}

Avram, Speranta ^{[4
]}

Mancas, Silvia ^{[5
]}

Careja, Valentin ^{[3
]}

Duda-Seiman, Corina ^{[1
]}

Putz, Mihai V. ^{[1
]}

Ciubotariu, Dan ^{[2
]}

机构：

[1] Univ W Timisoara, Fac Chem Biol Geog, Dept Chem, Timisoara, Romania

[2] Univ Med & Farm Timisoara, Fac Pharm, Timisoara, Romania

[3] Romanian Acad, Inst Chem Coriolan Dragulescu, Timisoara, Romania

[4] Univ Bucharest, Fac Biol, Dept Physiol & Biophys, Bucharest, Romania

[5] Univ Med & Farm Timisoara, Dept Med Ambulatory, Bucharest, Romania

来源：

JOURNAL OF THE SERBIAN CHEMICAL SOCIETY | 2011年 / 76卷 / 01期

关键词：

statins; molecular modelling; correlations; 3D-quantitative structure-biological activity; CHOLESTEROL; QSAR; STATINS;

D O I：

10.2298/JSC100601019D

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The 3D quantitative structure activity relationship for a series of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors based on the pyrrolylethyl-tetrahydropyranone scaffold was examined using the Minimal Topological Difference (MTD) method and comparative molecular similarity index analysis (CoMSIA). The studied compounds were of the tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one type. In clinical practice, HMG-CoA reductase inhibitors are usually referred to by the generic name statins. The analysis performed using the MID method showed that voluminous substituents produce a significant biological activity (R-CV(2) = 0.677 > 0.5; SEECV = = 0.319), while the CoMSIA method added useful information regarding the influence of the steric, electrostatic, hydrophobic, hydrogen bond donor, and acceptor properties on biological activity (R-CV(2) = 0.60; r(2) = 0.98).

引用

页码：85 / 99

页数：15

共 28 条

[21] INHIBITORS OF CHOLESTEROL-BIOSYNTHESIS .3. TETRAHYDRO-4-HYDROXY-6-[2-(1H-PYRROL-1-YL)ETHYL]-2H-PYRAN-2-ONE INHIBITORS OF HMG-COA REDUCTASE .2. EFFECTS OF INTRODUCING SUBSTITUENTS AT POSITIONS 3 AND 4 OF THE PYRROLE NUCLEUS [J].

ROTH, BD ;

BLANKLEY, CJ ;

CHUCHOLOWSKI, AW ;

FERGUSON, E ;

HOEFLE, ML ;

ORTWINE, DF ;

NEWTON, RS ;

SEKERKE, CS ;

SLISKOVIC, DR ;

STRATTON, CD ;

WILSON, MW .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :357-366

[22] Beyond the F test:: Effect size confidence intervals and tests of close fit in the analysis of variance and contrast analysis [J].

Steiger, JH .

PSYCHOLOGICAL METHODS, 2004, 9 (02) :164-182

[23]

Suh ME, 2002, B KOR CHEM SOC, V23, P417

[24] ARBITER: Arterial biology for the investigation of the treatment effects of reducing cholesterol - A randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness [J].

Taylor, AJ ;

Kent, SM ;

Flaherty, PJ ;

Coyle, LC ;

Markwood, TT ;

Vernalis, MN .

CIRCULATION, 2002, 106 (16) :2055-2060

[25] Three-dimensional quantitative structure (3-D QSAR) activity relationship studies on imidazolyl and N-pyrrolyl heptenoates as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitors by comparative molecular similarity indices analysis (CoMSIA) [J].

Thilagavathi, R ;

Kumar, R ;

Aparna, V ;

Sobhia, AE ;

Gopalakrishnan, B ;

Chakraborti, AK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (04) :1027-1032

[26] NEW DEVELOPMENTS IN LIPID-LOWERING THERAPY - THE ROLE OF INHIBITORS OF HYDROXYMETHYLGLUTARYL-COENZYME-A REDUCTASE [J].

TOBERT, JA .

CIRCULATION, 1987, 76 (03) :534-538

[27]

*TRIP ASS INC, 1988, SYBYL THEOR MAN VERS

[28] Update on statins: 2003 [J].

Vaughan, CJ ;

Gotto, AM .

CIRCULATION, 2004, 110 (07) :886-892

← 1 2 3 →