TY  - JOUR
AU  - Ramsay, Rona R.
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Uliassi, Elisa
AU  - Bolognesi, Maria Laura
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3148
AB  - Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.
PB  - Springeropen, London
T2  - Clinical and Translational Medicine
T1  - A perspective on multi-target drug discovery and design for complex diseases
VL  - 7
DO  - 10.1186/s40169-017-0181-2
ER  - 

@article{
author = "Ramsay, Rona R. and Popović-Nikolić, Marija and Nikolić, Katarina and Uliassi, Elisa and Bolognesi, Maria Laura",
year = "2018",
abstract = "Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.",
publisher = "Springeropen, London",
journal = "Clinical and Translational Medicine",
title = "A perspective on multi-target drug discovery and design for complex diseases",
volume = "7",
doi = "10.1186/s40169-017-0181-2"
}

Ramsay, R. R., Popović-Nikolić, M., Nikolić, K., Uliassi, E.,& Bolognesi, M. L.. (2018). A perspective on multi-target drug discovery and design for complex diseases. in Clinical and Translational Medicine
Springeropen, London., 7.
https://doi.org/10.1186/s40169-017-0181-2

Ramsay RR, Popović-Nikolić M, Nikolić K, Uliassi E, Bolognesi ML. A perspective on multi-target drug discovery and design for complex diseases. in Clinical and Translational Medicine. 2018;7.
doi:10.1186/s40169-017-0181-2 .

Ramsay, Rona R., Popović-Nikolić, Marija, Nikolić, Katarina, Uliassi, Elisa, Bolognesi, Maria Laura, "A perspective on multi-target drug discovery and design for complex diseases" in Clinical and Translational Medicine, 7 (2018),
https://doi.org/10.1186/s40169-017-0181-2 . .

TY  - JOUR
AU  - Hughes, Rebecca E.
AU  - Nikolić, Katarina
AU  - Ramsay, Rona R.
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2592
AB  - Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MID design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Neuroscience
T1  - One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug
VL  - 10
DO  - 10.3389/fnins.2016.00177
ER  - 

@article{
author = "Hughes, Rebecca E. and Nikolić, Katarina and Ramsay, Rona R.",
year = "2016",
abstract = "Alzheimer's Disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs (MTDs). Intended as an introduction for non-experts, this review describes the key MID design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch, and the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer's Disease are rasagiline, originally developed for the treatment of Parkinson's Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Neuroscience",
title = "One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug",
volume = "10",
doi = "10.3389/fnins.2016.00177"
}

Hughes, R. E., Nikolić, K.,& Ramsay, R. R.. (2016). One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. in Frontiers in Neuroscience
Frontiers Media Sa, Lausanne., 10.
https://doi.org/10.3389/fnins.2016.00177

Hughes RE, Nikolić K, Ramsay RR. One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. in Frontiers in Neuroscience. 2016;10.
doi:10.3389/fnins.2016.00177 .

Hughes, Rebecca E., Nikolić, Katarina, Ramsay, Rona R., "One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug" in Frontiers in Neuroscience, 10 (2016),
https://doi.org/10.3389/fnins.2016.00177 . .

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  - Bautista-Aguilera, Oscar M.
AU  - Samadi, Abdelouahid
AU  - Chioua, Mourad
AU  - Nikolić, Katarina
AU  - Filipić, Slavica
AU  - Agbaba, Danica
AU  - Soriano, Elena
AU  - de Andres, Lucia
AU  - Isabel Rodriguez-Franco, Maria
AU  - Alcaro, Stefano
AU  - Ramsay, Rona R.
AU  - Ortuso, Francesco
AU  - Yanez, Matilde
AU  - Marco-Contelles, Jose
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2113
AB  - On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Medicinal Chemistry
T1  - N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual
VL  - 57
IS  - 24
SP  - 10455
EP  - 10463
DO  - 10.1021/jm501501a
ER  - 

@article{
author = "Bautista-Aguilera, Oscar M. and Samadi, Abdelouahid and Chioua, Mourad and Nikolić, Katarina and Filipić, Slavica and Agbaba, Danica and Soriano, Elena and de Andres, Lucia and Isabel Rodriguez-Franco, Maria and Alcaro, Stefano and Ramsay, Rona R. and Ortuso, Francesco and Yanez, Matilde and Marco-Contelles, Jose",
year = "2014",
abstract = "On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Medicinal Chemistry",
title = "N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual",
volume = "57",
number = "24",
pages = "10455-10463",
doi = "10.1021/jm501501a"
}

Bautista-Aguilera, O. M., Samadi, A., Chioua, M., Nikolić, K., Filipić, S., Agbaba, D., Soriano, E., de Andres, L., Isabel Rodriguez-Franco, M., Alcaro, S., Ramsay, R. R., Ortuso, F., Yanez, M.,& Marco-Contelles, J.. (2014). N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual. in Journal of Medicinal Chemistry
Amer Chemical Soc, Washington., 57(24), 10455-10463.
https://doi.org/10.1021/jm501501a

Bautista-Aguilera OM, Samadi A, Chioua M, Nikolić K, Filipić S, Agbaba D, Soriano E, de Andres L, Isabel Rodriguez-Franco M, Alcaro S, Ramsay RR, Ortuso F, Yanez M, Marco-Contelles J. N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual. in Journal of Medicinal Chemistry. 2014;57(24):10455-10463.
doi:10.1021/jm501501a .

Bautista-Aguilera, Oscar M., Samadi, Abdelouahid, Chioua, Mourad, Nikolić, Katarina, Filipić, Slavica, Agbaba, Danica, Soriano, Elena, de Andres, Lucia, Isabel Rodriguez-Franco, Maria, Alcaro, Stefano, Ramsay, Rona R., Ortuso, Francesco, Yanez, Matilde, Marco-Contelles, Jose, "N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual" in Journal of Medicinal Chemistry, 57, no. 24 (2014):10455-10463,
https://doi.org/10.1021/jm501501a . .