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X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as ?1A-Adrenoceptor Antagonists.

ABSTRACT: Indole-arylpiperazine derivatives have exhibited good selectivity for the ?1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations and molecular docking using a homology model of the ?1A receptor. Compounds 1 and 3 form H-bonds networks to stabilize their three-dimensional structures, while C-H···? interactions play a significant role in the packing of 2. Based on DFT-optimized conformations, the HOMO-LUMO energy gaps and molecular electrostatic potential (MEP) were theoretically calculated at the B3LYP/6-311G (d, p) level of theory. Chemical reactivity increases in the order of 3 < 2 < 1, and the maximum positive region of the MEP maps is mainly localized over the NH group. The binding mechanisms of ligand-?1A-adrenoceptor complexes were illustrated by molecular docking. Binding to Gln177 of the second extracellular loop region via hydrogen bonds is likely to be essential for ?1A-selective antagonists. The present work sheds light on the studies of structure-activity-binding mechanism and aids in the design of ?1A antagonists with high selectivity.

SUBMITTER: Xu W

PROVIDER: S-EPMC6332402 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as α1A-Adrenoceptor Antagonists.

Xu Wei W Huang Jun-Jun JJ Shao Bin-Hao BH Xu Xing-Jie XJ Jiang Ren-Wang RW Yuan Mu M

Molecules (Basel, Switzerland) 20151030 11

Indole-arylpiperazine derivatives have exhibited good selectivity for the α1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations and molecular docking using a homology model of the α1A receptor. Compounds 1 and 3 form H-bonds networks to stabilize their three-dimensional structures, while C-H···π ...[more]

PMID: 26528963

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Dataset Information

X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as ?1A-Adrenoceptor Antagonists.

Publications

X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as α1A-Adrenoceptor Antagonists.

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