Synthesis of novel Hantzsch dihydropyridines and Biginelli dihydropyrimidines of biological interest: a 3D-QSAR study on their cytotoxicity

被引：26

作者：

Kumar, B. R. Prashantha ^{[1
]}

Masih, Pankaj ^{[1
]}

Karthikeyan, E. ^{[1
]}

Bansal, Ankur ^{[2
]}

Suja ^{[2
]}

Vijayan, Pottekad ^{[2
]}

机构：

[1] JSS Coll Pharm, Dept Pharmaceut Chem, Ootacamund 643001, TN, India

[2] JSS Coll Pharm, Dept Biotechnol, Ootacamund 643001, TN, India

来源：

MEDICINAL CHEMISTRY RESEARCH | 2010年 / 19卷 / 04期

关键词：

Dihydropyrimidines; Dihydropyridines; CoMFA; Cytotoxicity; CHEMISTRY; DEHYDROGENASE; VALIDATION; COMFA; FIELD; QSAR;

D O I：

10.1007/s00044-009-9195-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report a library consisting of some novel Hantzsch dihydropyridines and Biginelli dihydropyrimidines of biological interest as well as their synthesis and analysis. The important steps in the synthetic part were found to be Hantzsch and Biginelli multicomponent reactions. The synthesized compounds were screened for their in vitro antibacterial activity against two gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis. The title compounds did not exhibit potential antibacterial activity. Furthermore, compounds were subjected to in vitro cytotoxicity against Vero cells. Compounds exhibited weak, moderate, or high cytotoxicity. Compounds 4a, 4b, 4c, 4f, 4g, 4h, 4i, 7i, 7l, 7m, and 7r exhibited potential cytotoxicity. CoMFA study has resulted in the identification of structural features contributing toward their cytotoxicity.

引用

页码：344 / 363

页数：20

共 38 条

[1]

ANDREAS H, 1999, SOLID STATE NUCL MAG, V13, P231, DOI DOI 10.1016/S0926-2040(98)00090-3

[2] The tethered Biginelli condensation in natural product synthesis [J].

Aron, ZD ;

Overman, LE .

CHEMICAL COMMUNICATIONS, 2004, (03) :253-265

[3]

Biginelli P., 1893, GAZZ CHIM ITAL, V23, P360

[4]

BRUCE TC, 1966, BIOORGANIC MECH, V2

[5] VALIDATION OF THE GENERAL-PURPOSE TRIPOS 5.2 FORCE-FIELD [J].

CLARK, M ;

CRAMER, RD ;

VANOPDENBOSCH, N .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1989, 10 (08) :982-1012

[6]

Clark M., 1990, TETRAHEDRON COMPUT M, V3, P47, DOI [DOI 10.1016/0898-5529(90)90120-W, 10.1016/0898-5529(90)90120-W]

[7] CROSS-VALIDATION, BOOTSTRAPPING, AND PARTIAL LEAST-SQUARES COMPARED WITH MULTIPLE-REGRESSION IN CONVENTIONAL QSAR STUDIES [J].

CRAMER, RD ;

BUNCE, JD ;

PATTERSON, DE ;

FRANK, IE .

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS, 1988, 7 (01) :18-25

[8] COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA) .1. EFFECT OF SHAPE ON BINDING OF STEROIDS TO CARRIER PROTEINS [J].

CRAMER, RD ;

PATTERSON, DE ;

BUNCE, JD .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (18) :5959-5967

[9] Solid- and solution-phase synthesis of bioactive dihydropyrimidines [J].

Dallinger, D ;

Stadler, A ;

Kappe, CO .

PURE AND APPLIED CHEMISTRY, 2004, 76 (05) :1017-1024

[10] Synthesis and QSAR studies of 4-substituted phenyl-2,6-dimethyl-3, 5-bis-N-(substituted phenyl)carbamoyl-1,4-dihydropyridines as potential antitubercular agents [J].

Desai, B ;

Sureja, D ;

Naliapara, Y ;

Shah, A ;

Saxena, AK .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (08) :1993-1998

← 1 2 3 4 →