Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study

Chimenti, Franco; Secci, Daniela; Bolasco, Adriana; Chimenti, Paola; Granese, Arianna; Befani, Olivia; Turini, Paola; Alcaro, Stefano; Ortuso, Francesco

doi:10.1016/j.bmcl.2004.05.010

Cited by 93 publications

(45 citation statements)

References 37 publications

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“…1) and its derivatives are interesting from biological point of view because of the various medicinal applications. They are proved to be selective inhibitor of monoamine oxidase [4] and exhibit antibacterial activities [21]. Coumarin-3-carboxylic acid has been reported as a detector of hydroxyl radical generated chemically or by gamma radiation [22].…”

Section: Introductionmentioning

confidence: 99%

“…Coumarins generate strong interest stemming from their great physiological and biological activities, which is further exemplified by their roles as anticoagulants (dicoumarols and its derivatives, warfarin), spasmolytics [1], chemotherapeutics [2], biological inhibitors [3,4], antibacterial [5] and antifungal [6] agents, bio-analytical reagents [7] or as plant growth regulating agents [8][9][10][11][12]. With the purpose of reinforce the biological properties of coumarins their coordination ability to different transition metal and lanthanide ions has been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vibrational and theoretical study of coumarin-3-carboxylic acid binding mode in Ce(III) and Nd(III) complexes

Georgieva

Trendafilova

Kiefer

et al. 2007

Vibrational Spectroscopy

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vibrational and theoretical study of coumarin-3-carboxylic acid binding mode in Ce(III) and Nd(III) complexes

Georgieva

Trendafilova

Kiefer

et al. 2007

Vibrational Spectroscopy

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“…3-Acyl coumarin derivatives [41] have recently proven to be reversible and selective inhibitors of MAO-B, displaying IC 50 values in the submicromolar range, with derivatives bearing substituents at position 7 showing interesting results. Besides esuprone [42] and LU-53439 [43] (Fig.…”

mentioning

confidence: 99%

Lipophilicity Plays a Major Role in Modulating the Inhibition of Monoamine Oxidase B by 7‐Substituted Coumarins

Carotti

Altomare

Catto

et al. 2006

Chemistry & Biodiversity

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A series of coumarin derivatives (1-22), bearing at the 7-position ether, ketone, ester, carbamate, or amide functions of varying size and lipophilicity, were synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A and -B) inhibitory activities. Most of the compounds acted preferentially as MAO-B inhibitors, with IC(50) values in the micromolar to low-nanomolar range. A structure-activity-relationship (SAR) study highlighted lipophilicity as an important property modulating the MAO-B inhibition potency of 7-substituted coumarins, as shown by a linear correlation (n=20, r(2)=0.72) between pIC(50) and calculated log P values. The stability of ester-containing coumarin derivatives in rat plasma provided information on factors that either favor (lipophilicity) or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14 and 22) were selected to investigate how lipophilicity and enzymatic stability may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1-benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%) ex vivo rat-liver and striatal MAO-B activities 1 h after intraperitoneal administration of high doses (100 and 300 mumol kg(-1)), revealing its ability to cross the blood-brain barrier. At the same doses, liver and striatum MAO-A was less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in vitro. In contrast, the metabolically less stable derivative 14, bearing an isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory effects on MAO-A in both peripheral and brain tissues.

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“…5 There are many different structures of MAOIs due to the fact that the active sites of the MAO-A are still unknown today which limits the design of potent selective MAOIs. 6,7 The three-dimensional structures of both MAO-A and MAO-B are therefore of interest. However, both enzymes are bound to the outer mitochondrial membrane through a C-terminal polypeptide segment and this feature has made structural investigation by X-ray crystallography more difficult.…”

Section: Human Monoamine Oxidases a And B (Mao-a And B)mentioning

confidence: 99%

Synthesis of 3-benzyl-2-substituted quinoxalines as novel monoamine oxidase A inhibitors

Hassan

Khattab

Bekhit

et al. 2006

Bioorganic & Medicinal Chemistry Letters

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Inhibition of monoamine oxidases by coumarin-3-acyl derivatives: biological activity and computational study

Cited by 93 publications

References 37 publications

Vibrational and theoretical study of coumarin-3-carboxylic acid binding mode in Ce(III) and Nd(III) complexes

Vibrational and theoretical study of coumarin-3-carboxylic acid binding mode in Ce(III) and Nd(III) complexes

Lipophilicity Plays a Major Role in Modulating the Inhibition of Monoamine Oxidase B by 7‐Substituted Coumarins

Synthesis of 3-benzyl-2-substituted quinoxalines as novel monoamine oxidase A inhibitors

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