Three-dimensional pharmacophore hypotheses for the locust neuronal octopamine receptor (OAR3). Part 2: agonists

Hirashima, Akinori; Pan, Canping; Kuwano, Eiichi; Taniguchi, Eiji; Etō, Morifusa

doi:10.1016/s0968-0896(99)00057-7

Cited by 18 publications

(11 citation statements)

References 22 publications

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“…Taken together, an HpAr, three HpAls and an HBAl located on the molecule seem to be essential for OA-agonist activity. The hypotheses obtained here correspond those published previously against OA receptor 3 of locust nervous system using binding assay [5].…”

Section: Resultssupporting

confidence: 90%

“…In a previous application, we described the use of Catalyst/Hypo to derive a 4-and 5-feature hypothesis from a set of 17 octopamine (OA) antagonists [4] and 43 agonists [5], respectively. Threedimensional pharmacophore hypotheses were built from a set of 9 OA agonists responsible for the inhibition of sex-pheromone production in Helicoverpa armigera [6].…”

Section: Introductionmentioning

confidence: 99%

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Three-Dimensional Common-Feature Hypotheses for Octopamine Agonist 1-Arylimidazolidine-2-Thiones

Hirashima

Morimoto

Ohta

et al. 2002

IJMS

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Three-dimensional pharmacophore hypotheses were built from a set of 10 octopamine (OA) agonist 1-arylimidazole-2(3H)-thiones (AIHTs) and 1-arylimidazolidine-2-thiones (AITs). Among the ten common-featured models generated by program Catalyst/HipHop, a hypothesis including a hydrophobic aromatic (HpAr), three hydrophobic aliphatic (HpAl) and a hydrogen-bond acceptor lipid (HBAl) features was considered to be important in evaluating the OA-agonist activity. Active OA agonist 2,6-Et 2 AIT mapped well onto all the HpAr, HpAl and HBAl features of the hypothesis. On the other hand, inactive compound 2,6-Et 2 AIHT was shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies on OA agonists demonstrate that an HpAr, three HpAls and an HBAl sites located on the molecule seem to be essential for OA-agonist activity.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Common-Feature Hypotheses for Octopamine Agonist 1-Arylimidazolidine-2-Thiones

Hirashima

Morimoto

Ohta

et al. 2002

IJMS

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“…ABCB1 inhibitory activity data (IC 50 : Figure S1) of training set compounds span 4 orders of magnitude (from 50 to 100 000 nM), and these data were tested with the same assay (ADR accumulation assay in EMT6 ⁄ AR1.0 cells). All the compounds were optimized in DISCOVERY STUDIO 3.0 software (Accelrys Inc.) using the CHARMm-like force field (26)(27)(28). Conformations of training set compounds were generated using Generate Conformation module of DS running with best conformations option with 20 kcal ⁄ mol energy cutoff, and maximum number of conformations was set to 255.…”

Section: Pharmacophore Generation Using Hypogenmentioning

confidence: 99%

Pharmacophore‐Based Drug Design and Biological Evaluation of Novel ABCB1 Inhibitors

Zhang

Wei²,

et al. 2012

Chem Biol Drug Des

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Overexpression of ABCB1 is one of major barriers for multidrug resistance in chemotherapy and limits drug oral bioavailability. Inhibition of ABCB1 would sensitize multidrug resistance in clinical cancer chemotherapy. With this aim, a 3D pharmacophore model was created based on known ABCB1 inhibitors with correlation coefficient of 0.94, comprising three hydrophobic features and one hydrogen bond acceptor. It was further validated and used to search our in-house 3D database for potential ABCB1 inhibitors. The inhibitory activities of the best hits were evaluated by several biological assays, such as rhodamine 123 accumulation assay, chemosensitization assay, multidrug resistance 1-Madin-Darby canine kidney cells/Madin-Darby canine kidney cells permeability assay. Finally, compounds YZ-3 and YZ-16 were identified as potential leads to be developed in the designing of novel potent ABCB1 inhibitors.

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“…All other compounds were partial agonists, since they did not increase cAMP levels significantly, compared to OA ( Table 1). Compounds 22,23,32, and 43 were moderate octopaminergic agonists. However, they were poor inhibitors with respect to both calling behavior and pheromone production.…”

mentioning

confidence: 95%

The Pheromone Production of Female Plodia interpunctella Is Inhibited by Tyraminergic Antagonists

Hirashima

Kimizu

Shigeta

et al. 2004

Chemistry & Biodiversity

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Several compounds were found to suppress the calling behavior and in vitro pheromone biosynthesis of the Indian meal moth, Plodia interpunctella. The compounds were screened by means of a calling-behavior bioassay with female P. interpunctella. Five derivatives with activities in the nanomolar range were identified, in order of decreasing pheromonostatic activity: 4-hydroxybenzaldehyde semicarbazone (42) > 5-(4-methoxyphenyl)-1,3-oxazole (38) > 5-[4-(tert-butyl)phenyl]-1,3-oxazole (40) > 5-(3-methoxyphenyl)-1,3-oxazole (35) > 5-(4-cyanophenyl)-1,3-oxazole (36). These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis, as determined with isolated pheromone-gland preparations that incorporated [1-(14)C]sodium acetate in the presence of the so-called pheromone-biosynthesis-activating neuropeptide (PBAN). The non-additive effect of the inhibitor with antagonist (yohimbine) for the tyramine (TA) receptor suggests that it could be a tyraminergic antagonist. Three-dimensional (3D) computer models were built from a set of compounds. Among the common-featured models generated by the program Catalyst/HipHop, aromatic-ring (AR) and H-bond-acceptor-lipophilic (HBAl) features were considered to be essential for inhibitory activity in the calling behavior and in vitro pheromone biosynthesis. Active compounds, including yohimbine, mapped well onto all the AR and HBAl features of the hypothesis. Less-active compounds were shown to be unable to achieve an energetically favorable conformation, consistent with our 3D common-feature pharmacophore models. The present hypothesis demonstrates that calling behavior and PBAN-stimulated incorporation of radioactivity are inhibited by tyraminergic antagonists.

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Three-dimensional pharmacophore hypotheses for the locust neuronal octopamine receptor (OAR3). Part 2: agonists

Cited by 18 publications

References 22 publications

Three-Dimensional Common-Feature Hypotheses for Octopamine Agonist 1-Arylimidazolidine-2-Thiones

Three-Dimensional Common-Feature Hypotheses for Octopamine Agonist 1-Arylimidazolidine-2-Thiones

Pharmacophore‐Based Drug Design and Biological Evaluation of Novel ABCB1 Inhibitors

The Pheromone Production of Female Plodia interpunctella Is Inhibited by Tyraminergic Antagonists

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