Density functional and docking studies of retinoids for cancer treatment.
The retinoic acid receptor (RAR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily. The ligand-binding domain contains the ligand-dependent activation function. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids involved in the treatment of various cancers and skin diseases. There is thus considerable interest in synthetic retinoids with isotype selectivity and reduced side effects. In this work we have focused on the retinoid acid receptor and three of its panagonists. We have carried out density functional geometry optimizations at the B3LYP/6-31G* level, computed two types of atomic charges and also electrostatic potentials. A docking program was used to investigate the interactions between the receptor and the three ligands. A theoretically more potent inhibitor, which was obtained by modifying one of the retinoic acids investigated, is proposed.
Silva
Carlos H T P
CH
Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, São Carlos, SP, Brazil.
Almeida
Paulo
P
Taft
Carlton A
CA
D001665:Binding Sites; D045744:Cell Line, Tumor; D018398:Homeodomain Proteins; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008962:Models, Theoretical; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy*; D016011:Normal Distribution; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000737:chemistry; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors / Q000737:chemistry; D012176:Retinoids / Q000737:chemistry* / Q000494:pharmacology*; D012177:Retinol-Binding Proteins; D012984:Software; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry
D018398:Homeodomain Proteins; D008024:Ligands; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D012177:Retinol-Binding Proteins; D014157:Transcription Factors