Discovery of reversible selective monoamine oxidase B inhibitors with anti-acetylcholinesterase activity derived from 4-oxo-N-4-diphenyl butanamides
Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition. With the help of fragment-based drug desi...
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| Published in: | Future medicinal chemistry Vol. 15; no. 2; pp. 189 - 210 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
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Newlands Press Ltd
01-01-2023
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| Abstract | Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition.
With the help of fragment-based drug design, some 4-oxo-N-4-diphenyl butanamides were designed and synthesized as MAO-B inhibitors with anti-acetylcholinesterase (AChE) activity.
Compound
showed the best neuroprotection, with reversible selective MAO-B inhibition activity (IC
= 11.54 ± 0.64 nM). Compounds
,
,
,
and
(IC
= 20.90 ± 0.50, 17.25 ± 0.90, 15.85 ± 0.16, 16.81 ± 0.85 and 25.19 ± 0.17 nM, respectively) also appeared as potent and selective MAO-B inhibitors with anti-AChE activity.
The present study suggests potent, neuroprotective and nontoxic lead compounds as selective MAO-B inhibitors with anti-AChE activity. |
|---|---|
| AbstractList | Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition.
With the help of fragment-based drug design, some 4-oxo-N-4-diphenyl butanamides were designed and synthesized as MAO-B inhibitors with anti-acetylcholinesterase (AChE) activity.
Compound
showed the best neuroprotection, with reversible selective MAO-B inhibition activity (IC
= 11.54 ± 0.64 nM). Compounds
,
,
,
and
(IC
= 20.90 ± 0.50, 17.25 ± 0.90, 15.85 ± 0.16, 16.81 ± 0.85 and 25.19 ± 0.17 nM, respectively) also appeared as potent and selective MAO-B inhibitors with anti-AChE activity.
The present study suggests potent, neuroprotective and nontoxic lead compounds as selective MAO-B inhibitors with anti-AChE activity. |
| Author | Singh, Sushil K Jana, Srabanti Nasreen, Tania |
| AuthorAffiliation | 1Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India |
| AuthorAffiliation_xml | – name: 1Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India |
| Author_xml | – sequence: 1 givenname: Srabanti orcidid: 0000-0001-8582-6829 surname: Jana fullname: Jana, Srabanti organization: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India – sequence: 2 givenname: Tania surname: Nasreen fullname: Nasreen, Tania organization: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India – sequence: 3 givenname: Sushil K orcidid: 0000-0003-0473-5824 surname: Singh fullname: Singh, Sushil K organization: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36799336$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_crstbi_2024_100124 crossref_primary_10_3389_fnins_2023_1171866 |
| Cites_doi | 10.1016/j.bmc.2007.11.059 10.1039/C6RA00302H 10.1021/acs.jmedchem.7b01351 10.1192/bjp.135.3.216 10.1017/S1092852912000594 10.1021/j100078a035 10.1016/0006-2952(61)90145-9 10.1063/1.1730376 10.1080/07391102.2018.1508371 10.1073/pnas.85.13.4934 10.1016/S0223-5234(03)00012-6 10.1016/0960-894X(96)00072-8 10.1021/jo5008916 10.1016/S0021-9258(19)52451-6 10.1002/minf.201100076 10.1006/abio.1997.2392 10.1063/1.470117 10.1001/archpsyc.1987.01800170041007 10.1046/j.1471-4159.1999.0731127.x 10.1021/jm010894d 10.1063/1.467468 10.1038/bjc.1987.190 10.1016/j.bmc.2017.05.043 10.1021/jp003919d 10.1103/PhysRevA.31.1695 10.1111/j.1742-4658.2011.08386.x 10.1093/nar/28.1.235 10.1016/j.bbrc.2006.03.190 10.1016/0306-4522(94)90311-5 10.1021/jm300106z 10.1016/j.ejmech.2011.04.043 10.1016/j.bpj.2014.05.047 10.1063/1.3558787 |
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| Keywords | fragment-based drug design Alzheimer’s disease cholinesterase monoamine oxidase B |
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| References | e_1_3_3_30_1 Berthold MR (e_1_3_3_31_1) 2007 e_1_3_3_18_1 e_1_3_3_17_1 e_1_3_3_39_1 Nagatsu T (e_1_3_3_7_1) 2020 e_1_3_3_19_1 e_1_3_3_14_1 e_1_3_3_37_1 e_1_3_3_13_1 e_1_3_3_38_1 e_1_3_3_16_1 e_1_3_3_35_1 e_1_3_3_15_1 e_1_3_3_36_1 e_1_3_3_10_1 e_1_3_3_33_1 e_1_3_3_34_1 e_1_3_3_12_1 e_1_3_3_11_1 e_1_3_3_32_1 Shih JC (e_1_3_3_3_1) 1991; 4 e_1_3_3_6_1 e_1_3_3_9_1 e_1_3_3_8_1 e_1_3_3_29_1 e_1_3_3_28_1 e_1_3_3_25_1 e_1_3_3_24_1 e_1_3_3_27_1 e_1_3_3_26_1 e_1_3_3_21_1 e_1_3_3_20_1 e_1_3_3_5_1 e_1_3_3_23_1 e_1_3_3_4_1 e_1_3_3_22_1 |
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| SubjectTerms | Alzheimer’s disease cholinesterase fragment-based drug design Monoamine Oxidase - metabolism monoamine oxidase B Monoamine Oxidase Inhibitors - pharmacology Structure-Activity Relationship |
| Title | Discovery of reversible selective monoamine oxidase B inhibitors with anti-acetylcholinesterase activity derived from 4-oxo-N-4-diphenyl butanamides |
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