8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Abstract

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC 50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Haloperidol‐induced catalepsy as an animal model for parkinsonism: A systematic review of experimental studies

“…The variation in publications per year is important data. As noted, the haloperidol‐induced catalepsy model for parkinsonism was first applied in the early 1980s (Chiu et al., 1981; Pycock et al., 1982; Schallert & Teitelbaum, 1981; Scheel‐Krüger & Magelund, 1981) and is still widely used nowadays (Bhattamisra et al., 2020; Chaudhary & Dhande, 2020; Kabra et al., 2020; Łażewska et al., 2020; Olaya et al., 2020; Parambi et al., 2020; Pardo et al., 2020; Sanawar et al., 2020; Sharma et al., 2020; Sita et al., 2020). In fact, since 2000, the number of articles published using this model has increased and become more constant (Figure 2).…”

Biological Activities of Extracts from Ageratum fastigiatum: Phytochemical Study and In Silico Target Fishing Approach

“…The coumarins and monoterpenes drew attention because they could inhibit MAO and opioid receptors (▶ Table 3). In studies carried out by Olaya and coworkers [21], a synthetic coumarin showed MAOAi activity, and the results suggested that this compound could present anti-Parkinsonian activity related to MAOAi. The analgesic activity predicted is according to the ethnopharmacological use of the plant species and the biological studies reported in the literature (▶ Table 3).…”