FarFaR - Pharmacy Repository
University of Belgrade, Faculty of Pharmacy
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrillic)
    • Serbian (Latin)
  • Login
View Item 
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways

Authorized Users Only
2015
Authors
Nikolić, Katarina
Agbaba, Danica
Stark, Holger
Article (Published version)
Metadata
Show full item record
Abstract
In an effort to design dual acting compounds enhancing histaminergic neurotransmission in the central nervous system, a novel class of 35 non-imidazole histamine H-3 receptor (H3R) antagonists that simultaneously possess strong inhibitory potency on catabolic histamine N-methyltransferase (HMT), have been examined by 3D-QSAR study. For improved understanding, the crucial chemical functionalities for combined H3R/HMT activities 3D-QSAR pharmacophore models (H3R: R-2 (0.98), Q(2)(0.94), RMSE (0.171); and HMT: R-2 (0.80), Q(2) (0.60), RMSE (0.159) were developed. Pharmacophore for H3R antagonistic activity mainly differs from pharmacophore for HMT inhibiting activity in presence of specific lipophilic/steric components of the H3R pharmacophore, H-bond accepting components of the H3R pharmacophore, H-bond donating components of the HMT pharmacophore, and longer optimal distance between H-bond donor and steric hot spots in the H3R pharmacophore than in the HMT pharmacophore. Formed 3D-QSAR ...models were applied for design of novel piperidino-aminoquinoline hybrids as multitarget H3R/HMT ligands with potential impact in therapy of sleep-wake disorders and cognitive impairment. Designed compounds with 3D-QSAR predicted pKi (H3R) > 9.6 and (pKi (H3R) + pIC(50)(HMT)) > 16.8 were selected for further profiling. Virtual screening of ZINC database is performed against the most promising H3R/HMT ligand and top ranked compounds are tested by both 3D-QSAR models.

Keywords:
Drug design / 3D-QSAR / Histamine H-3 receptor / Histamine N-methyltransferase / Pharmacophore / Virtual screening
Source:
Journal of the Taiwan Institute of Chemical Engineers, 2015, 46, 15-29
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-172033)
  • Translational Research Innovation-Pharma (TRIP)
  • Else Kroner-Fresenius-Stiftung

DOI: 10.1016/j.jtice.2014.09.017

ISSN: 1876-1070

WoS: 000348959600002

Scopus: 2-s2.0-84920375608
[ Google Scholar ]
10
7
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2402
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
AU  - Stark, Holger
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2402
AB  - In an effort to design dual acting compounds enhancing histaminergic neurotransmission in the central nervous system, a novel class of 35 non-imidazole histamine H-3 receptor (H3R) antagonists that simultaneously possess strong inhibitory potency on catabolic histamine N-methyltransferase (HMT), have been examined by 3D-QSAR study. For improved understanding, the crucial chemical functionalities for combined H3R/HMT activities 3D-QSAR pharmacophore models (H3R: R-2 (0.98), Q(2)(0.94), RMSE (0.171); and HMT: R-2 (0.80), Q(2) (0.60), RMSE (0.159) were developed. Pharmacophore for H3R antagonistic activity mainly differs from pharmacophore for HMT inhibiting activity in presence of specific lipophilic/steric components of the H3R pharmacophore, H-bond accepting components of the H3R pharmacophore, H-bond donating components of the HMT pharmacophore, and longer optimal distance between H-bond donor and steric hot spots in the H3R pharmacophore than in the HMT pharmacophore. Formed 3D-QSAR models were applied for design of novel piperidino-aminoquinoline hybrids as multitarget H3R/HMT ligands with potential impact in therapy of sleep-wake disorders and cognitive impairment. Designed compounds with 3D-QSAR predicted pKi (H3R) > 9.6 and (pKi (H3R) + pIC(50)(HMT)) > 16.8 were selected for further profiling. Virtual screening of ZINC database is performed against the most promising H3R/HMT ligand and top ranked compounds are tested by both 3D-QSAR models.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of the Taiwan Institute of Chemical Engineers
T1  - Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways
VL  - 46
SP  - 15
EP  - 29
DO  - 10.1016/j.jtice.2014.09.017
ER  - 
@article{
author = "Nikolić, Katarina and Agbaba, Danica and Stark, Holger",
year = "2015",
abstract = "In an effort to design dual acting compounds enhancing histaminergic neurotransmission in the central nervous system, a novel class of 35 non-imidazole histamine H-3 receptor (H3R) antagonists that simultaneously possess strong inhibitory potency on catabolic histamine N-methyltransferase (HMT), have been examined by 3D-QSAR study. For improved understanding, the crucial chemical functionalities for combined H3R/HMT activities 3D-QSAR pharmacophore models (H3R: R-2 (0.98), Q(2)(0.94), RMSE (0.171); and HMT: R-2 (0.80), Q(2) (0.60), RMSE (0.159) were developed. Pharmacophore for H3R antagonistic activity mainly differs from pharmacophore for HMT inhibiting activity in presence of specific lipophilic/steric components of the H3R pharmacophore, H-bond accepting components of the H3R pharmacophore, H-bond donating components of the HMT pharmacophore, and longer optimal distance between H-bond donor and steric hot spots in the H3R pharmacophore than in the HMT pharmacophore. Formed 3D-QSAR models were applied for design of novel piperidino-aminoquinoline hybrids as multitarget H3R/HMT ligands with potential impact in therapy of sleep-wake disorders and cognitive impairment. Designed compounds with 3D-QSAR predicted pKi (H3R) > 9.6 and (pKi (H3R) + pIC(50)(HMT)) > 16.8 were selected for further profiling. Virtual screening of ZINC database is performed against the most promising H3R/HMT ligand and top ranked compounds are tested by both 3D-QSAR models.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of the Taiwan Institute of Chemical Engineers",
title = "Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways",
volume = "46",
pages = "15-29",
doi = "10.1016/j.jtice.2014.09.017"
}
Nikolić, K., Agbaba, D.,& Stark, H.. (2015). Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways. in Journal of the Taiwan Institute of Chemical Engineers
Elsevier Science BV, Amsterdam., 46, 15-29.
https://doi.org/10.1016/j.jtice.2014.09.017
Nikolić K, Agbaba D, Stark H. Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways. in Journal of the Taiwan Institute of Chemical Engineers. 2015;46:15-29.
doi:10.1016/j.jtice.2014.09.017 .
Nikolić, Katarina, Agbaba, Danica, Stark, Holger, "Pharmacophore modeling, drug design and virtual screening on multi-targeting procognitive agents approaching histaminergic pathways" in Journal of the Taiwan Institute of Chemical Engineers, 46 (2015):15-29,
https://doi.org/10.1016/j.jtice.2014.09.017 . .

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB
 

 

All of DSpaceCommunitiesAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB