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Computer‐aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy
Author(s) -
Silva Carlos H. T. P.,
Leopoldino Andreia M.,
Silva Eloiza H. T.,
Espinoza V. A. A.,
Taft C. A.
Publication year - 2005
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.20470
Subject(s) - ligand (biochemistry) , retinoic acid receptor , retinoic acid , docking (animal) , hydrogen bond , retinoid x receptor , retinoid , chemistry , receptor , combinatorial chemistry , retinoid x receptor alpha , molecule , stereochemistry , nuclear receptor , computational biology , biochemistry , biology , transcription factor , medicine , organic chemistry , gene , nursing
The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand‐binding domain contains the ligand‐dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6‐31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005