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

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41 Citations (Scopus)


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
Issue number9
Publication statusPublished - 2002 Jul 23
Externally publishedYes


ASJC Scopus subject areas

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

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