Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study

Won Jea Cho, Eui Ki Kim, Il Yeong Park, Eun Young Jeong, Tae Sung Kim, Thanh Nguyen Le, Dae Duk Kim, Eung Seok Lee

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A series of 58 3-arylisoquinoline antitumor agents were investigated for defining the pharmacophore model using comparative molecular field analysis (CoMFA) program. The studied compounds related to bioisostere of benzophenanthridine alkaloid were synthesized and evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). In order to perform the systematic molecular modeling study of these compounds, the conformational search was carried out based on the single X-ray crystallographic structure of 7,8-dimethoxy-3-phenylisoquinolin-(2H)-one (2). Interestingly, two types of structures having different dihedral angles between the isoquinoline ring and 3-aryl ring were found in the crystals. Therefore, CoMFA was performed two different, overlapping ways. The alignments of the structures were based on the common isoquinoline ring and 3-aryl ring. The 3-D-quantitative structure-activity relationship study resulted in significant cross-validated, conventional r2 values equal to 0.715 and 0.927, respectively.

Original languageEnglish
Pages (from-to)2953-2961
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume10
Issue number9
DOIs
Publication statusPublished - 2002 Jul 23
Externally publishedYes

Fingerprint

Molecular modeling
Antineoplastic Agents
Benzophenanthridines
Quantitative Structure-Activity Relationship
Dihedral angle
Cytotoxicity
Alkaloids
Tumors
Cells
X-Rays
X rays
Lung
Crystals
Neoplasms
isoquinoline

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study. / Cho, Won Jea; Kim, Eui Ki; Park, Il Yeong; Jeong, Eun Young; Kim, Tae Sung; Le, Thanh Nguyen; Kim, Dae Duk; Lee, Eung Seok.

In: Bioorganic and Medicinal Chemistry, Vol. 10, No. 9, 23.07.2002, p. 2953-2961.

Research output: Contribution to journalArticle

Cho, Won Jea ; Kim, Eui Ki ; Park, Il Yeong ; Jeong, Eun Young ; Kim, Tae Sung ; Le, Thanh Nguyen ; Kim, Dae Duk ; Lee, Eung Seok. / Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study. In: Bioorganic and Medicinal Chemistry. 2002 ; Vol. 10, No. 9. pp. 2953-2961.
@article{77199640ebce45ffaf676bea9bd68668,
title = "Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study",
abstract = "A series of 58 3-arylisoquinoline antitumor agents were investigated for defining the pharmacophore model using comparative molecular field analysis (CoMFA) program. The studied compounds related to bioisostere of benzophenanthridine alkaloid were synthesized and evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). In order to perform the systematic molecular modeling study of these compounds, the conformational search was carried out based on the single X-ray crystallographic structure of 7,8-dimethoxy-3-phenylisoquinolin-(2H)-one (2). Interestingly, two types of structures having different dihedral angles between the isoquinoline ring and 3-aryl ring were found in the crystals. Therefore, CoMFA was performed two different, overlapping ways. The alignments of the structures were based on the common isoquinoline ring and 3-aryl ring. The 3-D-quantitative structure-activity relationship study resulted in significant cross-validated, conventional r2 values equal to 0.715 and 0.927, respectively.",
author = "Cho, {Won Jea} and Kim, {Eui Ki} and Park, {Il Yeong} and Jeong, {Eun Young} and Kim, {Tae Sung} and Le, {Thanh Nguyen} and Kim, {Dae Duk} and Lee, {Eung Seok}",
year = "2002",
month = "7",
day = "23",
doi = "10.1016/S0968-0896(02)00137-2",
language = "English",
volume = "10",
pages = "2953--2961",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "9",

}

TY - JOUR

T1 - Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study

AU - Cho, Won Jea

AU - Kim, Eui Ki

AU - Park, Il Yeong

AU - Jeong, Eun Young

AU - Kim, Tae Sung

AU - Le, Thanh Nguyen

AU - Kim, Dae Duk

AU - Lee, Eung Seok

PY - 2002/7/23

Y1 - 2002/7/23

N2 - A series of 58 3-arylisoquinoline antitumor agents were investigated for defining the pharmacophore model using comparative molecular field analysis (CoMFA) program. The studied compounds related to bioisostere of benzophenanthridine alkaloid were synthesized and evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). In order to perform the systematic molecular modeling study of these compounds, the conformational search was carried out based on the single X-ray crystallographic structure of 7,8-dimethoxy-3-phenylisoquinolin-(2H)-one (2). Interestingly, two types of structures having different dihedral angles between the isoquinoline ring and 3-aryl ring were found in the crystals. Therefore, CoMFA was performed two different, overlapping ways. The alignments of the structures were based on the common isoquinoline ring and 3-aryl ring. The 3-D-quantitative structure-activity relationship study resulted in significant cross-validated, conventional r2 values equal to 0.715 and 0.927, respectively.

AB - A series of 58 3-arylisoquinoline antitumor agents were investigated for defining the pharmacophore model using comparative molecular field analysis (CoMFA) program. The studied compounds related to bioisostere of benzophenanthridine alkaloid were synthesized and evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). In order to perform the systematic molecular modeling study of these compounds, the conformational search was carried out based on the single X-ray crystallographic structure of 7,8-dimethoxy-3-phenylisoquinolin-(2H)-one (2). Interestingly, two types of structures having different dihedral angles between the isoquinoline ring and 3-aryl ring were found in the crystals. Therefore, CoMFA was performed two different, overlapping ways. The alignments of the structures were based on the common isoquinoline ring and 3-aryl ring. The 3-D-quantitative structure-activity relationship study resulted in significant cross-validated, conventional r2 values equal to 0.715 and 0.927, respectively.

UR - http://www.scopus.com/inward/record.url?scp=0036311397&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036311397&partnerID=8YFLogxK

U2 - 10.1016/S0968-0896(02)00137-2

DO - 10.1016/S0968-0896(02)00137-2

M3 - Article

C2 - 12110317

AN - SCOPUS:0036311397

VL - 10

SP - 2953

EP - 2961

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 9

ER -