Benzo[]tiophen-3-ol Derivatives As Effective Inhibitors of Human Monoamine Oxidase: Design, Synthesis, and Biological Activity

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2019 Aug 20

PMID 31422706

Citations 7

Authors

Paolo Guglielmi

Daniela Secci

Anel Petzer

Donatella Bagetta

Paola Chimenti

Giulia Rotondi

Claudio Ferrante

Lucia Recinella

Sheila Leone

Stefano Alcaro

Gokhan Zengin

Jacobus P Petzer

Francesco Ortuso

Simone Carradori

Affiliations

Soon will be listed here.

Abstract

A series of benzo[]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors as well as in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed.

Citing Articles

Scaffold-Hopping Strategies in Aurone Optimization: A Comprehensive Review of Synthetic Procedures and Biological Activities of Nitrogen and Sulfur Analogues.

La Monica G, Alamia F, Bono A, Lauria A, Martorana A Molecules. 2024; 29(12).

PMID: 38930878 PMC: 11206683. DOI: 10.3390/molecules29122813.

An Overview of the Pharmacological Activities and Synthesis of Benzothiophene Derivatives.

Pathak S, Singh A, Sharma R, Pandey R Med Chem. 2024; 20(9):839-854.

PMID: 38920062 DOI: 10.2174/0115734064315107240603055845.

Facile synthesis of substituted 2-aroylbenzo[]thiophen-3-ols to form novel triazole hybrids using click chemistry.

Mukhtar A, Hussain A, Younas F, Yousuf S, Saeed M RSC Adv. 2024; 14(15):10270-10279.

PMID: 38549793 PMC: 10976476. DOI: 10.1039/d4ra01146e.

Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer's Disease.

Bagan A, Rodriguez-Arevalo S, Taboada-Jara T, Grinan-Ferre C, Pallas M, Brocos-Mosquera I Pharmaceutics. 2023; 15(10).

PMID: 37896141 PMC: 10610545. DOI: 10.3390/pharmaceutics15102381.

New Insights on the Activity and Selectivity of MAO-B Inhibitors through In Silico Methods.

Pacureanu L, Bora A, Crisan L Int J Mol Sci. 2023; 24(11).

PMID: 37298535 PMC: 10253494. DOI: 10.3390/ijms24119583.

References

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

Lamensdorf I, Eisenhofer G, Harvey-White J, Nechustan A, Kirk K, Kopin I . 3,4-Dihydroxyphenylacetaldehyde potentiates the toxic effects of metabolic stress in PC12 cells. Brain Res. 2000; 868(2):191-201. DOI: 10.1016/s0006-8993(00)02309-x. View

Lee J, Chang C, Liu I, CHI T, Yu H, Cheng J . Changes in endogenous monoamines in aged rats. Clin Exp Pharmacol Physiol. 2001; 28(4):285-9. DOI: 10.1046/j.1440-1681.2001.03439.x. View

Halliwell B, Clement M, Ramalingam J, Long L . Hydrogen peroxide. Ubiquitous in cell culture and in vivo?. IUBMB Life. 2001; 50(4-5):251-7. DOI: 10.1080/713803727. View

Binda C, Li M, Hubalek F, Restelli N, Edmondson D, Mattevi A . Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc Natl Acad Sci U S A. 2003; 100(17):9750-5. PMC: 187837. DOI: 10.1073/pnas.1633804100. View

Brunetti L, Michelotto B, Orlando G, Recinella L, Di Nisio C, Ciabattoni G . Aging increases amyloid beta-peptide-induced 8-iso-prostaglandin F2alpha release from rat brain. Neurobiol Aging. 2003; 25(1):125-9. DOI: 10.1016/s0197-4580(03)00038-1. View

Son S, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T . Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors. Proc Natl Acad Sci U S A. 2008; 105(15):5739-44. PMC: 2311356. DOI: 10.1073/pnas.0710626105. View

Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F . Chalcones: a valid scaffold for monoamine oxidases inhibitors. J Med Chem. 2009; 52(9):2818-24. DOI: 10.1021/jm801590u. View

Grimsby J, Chen K, Wang L, Lan N, Shih J . Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Proc Natl Acad Sci U S A. 1991; 88(9):3637-41. PMC: 51507. DOI: 10.1073/pnas.88.9.3637. View

10.

Liu Y, Wu W, Lu Y, Lai Y, Hou W . Antioxidant and amine oxidase inhibitory activities of hydroxyurea. Biosci Biotechnol Biochem. 2010; 74(6):1256-60. DOI: 10.1271/bbb.100096. View

11.

Bolasco A, Carradori S, Fioravanti R . Focusing on new monoamine oxidase inhibitors. Expert Opin Ther Pat. 2010; 20(7):909-39. DOI: 10.1517/13543776.2010.495716. View

12.

Wimbiscus M, Kostenko O, Malone D . MAO inhibitors: risks, benefits, and lore. Cleve Clin J Med. 2010; 77(12):859-82. DOI: 10.3949/ccjm.77a.09103. View

13.

Budimir A . Metal ions, Alzheimer's disease and chelation therapy. Acta Pharm. 2011; 61(1):1-14. DOI: 10.2478/v10007-011-0006-6. View

14.

Chan S, Low K, Yang C, Cheung S, Che C . Iron-ligand coordination in tandem radical cyclizations: synthesis of benzo[b]thiophenes by a one-pot reaction of iron 1,3-diketone complexes with 2-thiosalicylic acids. Chemistry. 2011; 17(17):4709-14. DOI: 10.1002/chem.201100377. View

15.

Ward R, Dexter D, Crichton R . Chelating agents for neurodegenerative diseases. Curr Med Chem. 2012; 19(17):2760-72. DOI: 10.2174/092986712800609689. View

16.

Carradori S, Secci D, Bolasco A, Chimenti P, DAscenzio M . Patent-related survey on new monoamine oxidase inhibitors and their therapeutic potential. Expert Opin Ther Pat. 2012; 22(7):759-801. DOI: 10.1517/13543776.2012.698613. View

17.

Kannan N, Guruvayoorappan C . Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators. Int Immunopharmacol. 2013; 16(1):57-66. DOI: 10.1016/j.intimp.2013.03.008. View

18.

Carradori S, DAscenzio M, Chimenti P, Secci D, Bolasco A . Selective MAO-B inhibitors: a lesson from natural products. Mol Divers. 2013; 18(1):219-43. DOI: 10.1007/s11030-013-9490-6. View

19.

Charan J, Kantharia N . How to calculate sample size in animal studies?. J Pharmacol Pharmacother. 2013; 4(4):303-6. PMC: 3826013. DOI: 10.4103/0976-500X.119726. View

20.

van Heesch F, Prins J, Konsman J, Korte-Bouws G, Westphal K, Rybka J . Lipopolysaccharide increases degradation of central monoamines: an in vivo microdialysis study in the nucleus accumbens and medial prefrontal cortex of mice. Eur J Pharmacol. 2014; 725:55-63. DOI: 10.1016/j.ejphar.2014.01.014. View