(S)-N-Benzyl-1-phenyl-3,4-dihydroisoqunoline-2(1H)-carboxamide Derivatives, Multi-Target Inhibitors of Monoamine Oxidase and Cholinesterase: Design, Synthesis, and Biological Activity

被引：4

作者：

Jin, Qing-Hao ^{[1
]}

Zhang, Li-Ping ^{[1
]}

Zhang, Shan-Shan ^{[2
]}

Zhuang, Dai-Na ^{[1
]}

Zhang, Chu-Yu ^{[1
]}

Zheng, Zhou-Jun ^{[1
]}

Guan, Li-Ping ^{[2
]}

机构：

[1] Zhejiang Pharmaceut Univ, Coll Nursing, Ningbo 315153, Peoples R China

[2] Zhejiang Ocean Univ, Food & Pharm Coll, Zhoushan 316022, Peoples R China

来源：

MOLECULES | 2023年 / 28卷 / 04期

关键词：

3; 4-dihydroisoquinoline; carboxamide derivatives; monoamine oxidase; cholinesterase; cytotoxicity; molecular docking; ALZHEIMERS-DISEASE; ISOQUINOLINE; ALKALOIDS;

D O I：

10.3390/molecules28041654

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives was synthesized and evaluated for inhibitory activity against monoamine oxidase (MAO)-A and-B, acetylcholine esterase (AChE), and butyrylcholine esterase (BChE). Four compounds (2i, 2p, 2t, and 2v) showed good inhibitory activity against both MAO-A and MAO-B, and two compounds (2d and 2j) showed selective inhibitory activity against MAO-A, with IC50 values of 1.38 and 2.48 mu M, respectively. None of the compounds showed inhibitory activity against AChE; however, 12 compounds showed inhibitory activity against BChE. None of the active compounds showed cytotoxicity against L929cells. Molecular docking revealed several important interactions between the active analogs and amino acid residues of the protein receptors. This research paves the way for further study aimed at designing MAO and ChE inhibitors for the treatment of depression and neurodegenerative disorders.

引用

页数：17

共 39 条

[1] Synthesis, biological investigation and molecular docking study of N-malonyl-1,2-dihydroisoquinoline derivatives as brain specific and shelf-stable MAO inhibitors [J].

Abd El-Gaber, Mohammed K. ;

Hassan, Hoda Y. ;

Mahfouz, Nadia M. ;

Farag, Hassan H. ;

Bekhit, Adnan A. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 93 :481-491

[2] Isolation, derivatization, in-vitro, and in-silico studies of potent butyrylcholinesterase inhibitors from Berberis parkeriana Schneid [J].

Ali, Rabia ;

Atia-tul-Wahab ;

Wajid, Sheeba ;

Khan, Maria Aqeel ;

Yousuf, Sammer ;

Shaikh, Muniza ;

Laghari, Gul Hassan ;

Atta-ur Rahman ;

Choudhary, M. Iqbal .

BIOORGANIC CHEMISTRY, 2022, 127

[3] Chlorination of Aliphatic Primary Alcohols via Triphosgene-Triethylamine Activation [J].

Ayala, Caitlan E. ;

Villalpando, Andres ;

Nguyen, Alex L. ;

McCandless, Gregory T. ;

Kartika, Rendy .

ORGANIC LETTERS, 2012, 14 (14) :3676-3679

[4] Selective inhibition of monoamine oxidase A by chelerythrine, an isoquinoline alkaloid [J].

Baek, Seung Cheol ;

Ryu, Hyung Won ;

Kang, Myung-Gyun ;

Lee, Hanna ;

Park, Daeui ;

Cho, Myoung-Lae ;

Oh, Sei-Ryang ;

Kim, Hoon .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (14) :2403-2407

[5] N-Hydroxy-N-Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases [J].

Bautista-Aguilera, Oscar M. ;

Alonso, Jose M. ;

Catto, Marco ;

Iriepa, Isabel ;

Knez, Damijan ;

Gobec, Stanislav ;

Marco-Contelles, Jose .

MOLECULES, 2022, 27 (21)

[6] Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors [J].

Behl, Tapan ;

Kaur, Dapinder ;

Sehgal, Aayush ;

Singh, Sukhbir ;

Sharma, Neelam ;

Zengin, Gokhan ;

Andronie-Cioara, Felicia Liana ;

Toma, Mirela Marioara ;

Bungau, Simona ;

Bumbu, Adrian Gheorghe .

MOLECULES, 2021, 26 (12)

[7] INHIBITION OF MONOAMINE OXIDASE-A AND MONOAMINE OXIDASE-B BY SIMPLE ISOQUINOLINE ALKALOIDS - RACEMIC AND OPTICALLY-ACTIVE 1,2,3,4-TETRAHYDRO-ISOQUINOLINE, 3,4-DIHYDRO-ISOQUINOLINE, AND FULLY AROMATIC ISOQUINOLINE [J].

BEMBENEK, ME ;

ABELL, CW ;

CHRISEY, LA ;

ROZWADOWSKA, MD ;

GESSNER, W ;

BROSSI, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (01) :147-152

[8] Monoamine oxidase inhibitors: Promising therapeutic agents for Alzheimer's disease (Review) [J].

Cai, Zhiyou .

MOLECULAR MEDICINE REPORTS, 2014, 9 (05) :1533-1541

[9] Natural Products Inhibitors of Monoamine Oxidases-Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma [J].

Chaurasiya, Narayan D. ;

Leon, Francisco ;

Muhammad, Ilias ;

Tekwani, Babu L. .

MOLECULES, 2022, 27 (13)

[10] Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B [J].

Chaurasiya, Narayan D. ;

Midiwo, Jacob ;

Pandey, Pankaj ;

Bwire, Regina N. ;

Doerksen, Robert J. ;

Muhammad, Ilias ;

Tekwani, Babu L. .

MOLECULES, 2020, 25 (22)

← 1 2 3 4 →