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. 2019 Sep 1;39(3):491-501.
doi: 10.7705/biomedica.4299.

Coumarin analogue 3-methyl-7H-furo[3,2-g] chromen-7-one as a possible antiparkinsonian agent

[Article in English, Spanish]
María Del Pilar Olaya  1 , Nadezdha Esperanza Vergel, José Luis López, María Dolores Viña, Mario Francisco Guerrero
Affiliations

Coumarin analogue 3-methyl-7H-furo[3,2-g] chromen-7-one as a possible antiparkinsonian agent

[Article in English, Spanish]
María Del Pilar Olaya et al. Biomedica. .

Abstract
in English, Spanish, Spanish

Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B.

Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity.

Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively.

Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity.

Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Introducción.: El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B.

Objetivo.: Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante.

Materiales y métodos.: Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005.

Resultados.: El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes.

Conclusión.: Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Keywords: Parkinson’s disease; monoamine oxidase; coumarins; models; animal; reserpine; levodopa; haloperidol; antioxidants.

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Conflict of interest statement

Conflicts of interest: The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. Structure of 3-methyl-7H-furo[3,2-g]-chromen-7-one (FCS005)
Figure 2
Figure 2. Mice not pretreated with reserpine. Effects on motor activity of the animals at 1.5 h (a) and 23.5 h (b) after administration of FCS005, selegiline or vehicle (0.1 mL/10 g body weight). * p<0.05 compared to the control group (n=7-9)
Figure 3
Figure 3. Reserpine model. Effects of administration of FCS005, selegiline or vehicle (0.1 mL/10 g body weight) on motor activity of the animals at 2 h (a) and 24 h (b) after administration of reserpine. * p<0.05 compared to the control group (n=7-9)
Figure 4
Figure 4. Effect of L-dopa/carbidopa and MAO-B inhibitors. Effects of the administration of levodopa/carbidopa (100/10 mg/kg) plus FCS005 (100 mg/kg), control (0 mg/kg) or selegiline (10 mg/kg) on motor activity at 2 h (a) and 24 h (b) after the administration of reserpine. * p<0.05 compared to control group (n=7-9)
Figure 5
Figure 5. Anti-cataleptic effects. Catalepsy in mice was assessed using the horizontal bar test. Effects of administration of levodopa/carbidopa (400/40 mg/kg), FCS005 (100 mg/kg) or control (0 mg/kg) on catalepsy induced by haloperidol (3 mg/kg) at 60 min * p<0.05 compared to the control group (n=8)
Figure 6
Figure 6. Antioxidant activity. Effect of FCS005 (50 mg/kg), control (0 mg/kg) or levodopa/ carbidopa (400/40 mg/kg) on (a) lipid peroxidation and (b) the oxidation of carbonyl groups of proteins in brain homogenates of mice treated with haloperidol (1 mg/kg) for 10 days * p<0.05 compared to the control group (n=8)
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