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 . .

TY  - JOUR
AU  - Nikolić, Katarina
AU  - Mavridis, Lazaros
AU  - Bautista-Aguilera, Oscar M.
AU  - Marco-Contelles, Jose
AU  - Stark, Holger
AU  - Carreiras, Maria do Carmo
AU  - Rossi, Ilaria
AU  - Massarelli, Paola
AU  - Agbaba, Danica
AU  - Ramsay, Rona R.
AU  - Mitchell, John B. O.
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2395
AB  - Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H-3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).
PB  - Springer, Dordrecht
T2  - Journal of Computer-Aided Molecular Design
T1  - Predicting targets of compounds against neurological diseases using cheminformatic methodology
VL  - 29
IS  - 2
SP  - 183
EP  - 198
DO  - 10.1007/s10822-014-9816-1
ER  - 

@article{
author = "Nikolić, Katarina and Mavridis, Lazaros and Bautista-Aguilera, Oscar M. and Marco-Contelles, Jose and Stark, Holger and Carreiras, Maria do Carmo and Rossi, Ilaria and Massarelli, Paola and Agbaba, Danica and Ramsay, Rona R. and Mitchell, John B. O.",
year = "2015",
abstract = "Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H-3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).",
publisher = "Springer, Dordrecht",
journal = "Journal of Computer-Aided Molecular Design",
title = "Predicting targets of compounds against neurological diseases using cheminformatic methodology",
volume = "29",
number = "2",
pages = "183-198",
doi = "10.1007/s10822-014-9816-1"
}

Nikolić, K., Mavridis, L., Bautista-Aguilera, O. M., Marco-Contelles, J., Stark, H., Carreiras, M. d. C., Rossi, I., Massarelli, P., Agbaba, D., Ramsay, R. R.,& Mitchell, J. B. O.. (2015). Predicting targets of compounds against neurological diseases using cheminformatic methodology. in Journal of Computer-Aided Molecular Design
Springer, Dordrecht., 29(2), 183-198.
https://doi.org/10.1007/s10822-014-9816-1

Nikolić K, Mavridis L, Bautista-Aguilera OM, Marco-Contelles J, Stark H, Carreiras MDC, Rossi I, Massarelli P, Agbaba D, Ramsay RR, Mitchell JBO. Predicting targets of compounds against neurological diseases using cheminformatic methodology. in Journal of Computer-Aided Molecular Design. 2015;29(2):183-198.
doi:10.1007/s10822-014-9816-1 .

Nikolić, Katarina, Mavridis, Lazaros, Bautista-Aguilera, Oscar M., Marco-Contelles, Jose, Stark, Holger, Carreiras, Maria do Carmo, Rossi, Ilaria, Massarelli, Paola, Agbaba, Danica, Ramsay, Rona R., Mitchell, John B. O., "Predicting targets of compounds against neurological diseases using cheminformatic methodology" in Journal of Computer-Aided Molecular Design, 29, no. 2 (2015):183-198,
https://doi.org/10.1007/s10822-014-9816-1 . .

TY  - JOUR
AU  - Nikolić, Katarina
AU  - Filipić, Slavica
AU  - Agbaba, Danica
AU  - Stark, Holger
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2196
AB  - The histamine H-3 receptor (H3R) is an important modulator of numerous central control mechanisms. Novel lead optimizations for H3R antagonists/inverse agonists involved studies of structure-activity relationships, cross-affinities, and pharmacokinetic properties of promising ligands. Blockade of inhibitory histamine H-3 autoreceptors reinforces histaminergic transmission, while antagonism of H-3 heteroreceptors accelerates the corticolimbic liberation of acetylcholine, norepinephrine, glutamate, dopamine, serotonin and gamma-aminobutyric acid (GABA). The H3R positioned at numerous neurotransmission crossroads indicates therapeutic applications of small-molecule H3R modulators in a number of psychiatric and neurodegenerative diseases with various clinical candidates available. Dual target drugs displaying H3R antagonism/inverse agonism with inhibition of acetylcholine esterase (AChE), histamine N-methyltransferase (HMT), or serotonin transporter (SERT) are novel class of procognitive agents. Main chemical diversities, pharmacophores, and pharmacological profiles of procognitive agents acting as H3R antagonists/inverse agonists and dual H3R antagonists/inverse agonists with inhibiting activity on AChE, HMT, or SERT are highlighted here.
PB  - Wiley, Hoboken
T2  - CNS Neuroscience & Therapeutics
T1  - Procognitive Properties of Drugs with Single and Multitargeting H-3 Receptor Antagonist Activities
VL  - 20
IS  - 7
SP  - 613
EP  - 623
DO  - 10.1111/cns.12279
ER  - 

@article{
author = "Nikolić, Katarina and Filipić, Slavica and Agbaba, Danica and Stark, Holger",
year = "2014",
abstract = "The histamine H-3 receptor (H3R) is an important modulator of numerous central control mechanisms. Novel lead optimizations for H3R antagonists/inverse agonists involved studies of structure-activity relationships, cross-affinities, and pharmacokinetic properties of promising ligands. Blockade of inhibitory histamine H-3 autoreceptors reinforces histaminergic transmission, while antagonism of H-3 heteroreceptors accelerates the corticolimbic liberation of acetylcholine, norepinephrine, glutamate, dopamine, serotonin and gamma-aminobutyric acid (GABA). The H3R positioned at numerous neurotransmission crossroads indicates therapeutic applications of small-molecule H3R modulators in a number of psychiatric and neurodegenerative diseases with various clinical candidates available. Dual target drugs displaying H3R antagonism/inverse agonism with inhibition of acetylcholine esterase (AChE), histamine N-methyltransferase (HMT), or serotonin transporter (SERT) are novel class of procognitive agents. Main chemical diversities, pharmacophores, and pharmacological profiles of procognitive agents acting as H3R antagonists/inverse agonists and dual H3R antagonists/inverse agonists with inhibiting activity on AChE, HMT, or SERT are highlighted here.",
publisher = "Wiley, Hoboken",
journal = "CNS Neuroscience & Therapeutics",
title = "Procognitive Properties of Drugs with Single and Multitargeting H-3 Receptor Antagonist Activities",
volume = "20",
number = "7",
pages = "613-623",
doi = "10.1111/cns.12279"
}

Nikolić, K., Filipić, S., Agbaba, D.,& Stark, H.. (2014). Procognitive Properties of Drugs with Single and Multitargeting H-3 Receptor Antagonist Activities. in CNS Neuroscience & Therapeutics
Wiley, Hoboken., 20(7), 613-623.
https://doi.org/10.1111/cns.12279

Nikolić K, Filipić S, Agbaba D, Stark H. Procognitive Properties of Drugs with Single and Multitargeting H-3 Receptor Antagonist Activities. in CNS Neuroscience & Therapeutics. 2014;20(7):613-623.
doi:10.1111/cns.12279 .

Nikolić, Katarina, Filipić, Slavica, Agbaba, Danica, Stark, Holger, "Procognitive Properties of Drugs with Single and Multitargeting H-3 Receptor Antagonist Activities" in CNS Neuroscience & Therapeutics, 20, no. 7 (2014):613-623,
https://doi.org/10.1111/cns.12279 . .