Fiscalin Derivatives as Potential Neuroprotective Agents

Abstract

Neurodegenerative diseases (ND) share common molecular/cellular mechanisms that contribute to their progression and pathogenesis. In this sense, we are here proposing new neuroprotection strategies by using marine-derived compounds as fiscalins. This work aims to evaluate the protective effects of fiscalin derivatives towards 1-methyl-4-phenylpyridinium (MPP+)- and iron (III)-induced cytotoxicity in differentiated SH-SY5Y cells, an in vitro disease model to study ND; and on P-glycoprotein (P-gp) transport activity, an efflux pump of drugs and neurotoxins. SH-SY5Y cells were simultaneously exposed to MPP+ or iron (III), and noncytotoxic concentrations of 18 fiscalin derivatives (0–25 μM), being the cytotoxic effect of both MPP+ and iron (III) evaluated 24 and 48 h after exposure. Fiscalins 1a and 1b showed a significant protective effect against MPP+-induced cytotoxicity and fiscalins 1b, 2b, 4 and 5 showed a protective effect against iron (III)-induced cytotoxicity. Fiscalins 4 and 5 caused a significant P-gp inhibition, while fiscalins 1c, 2a, 2b, 6 and 11 caused a modest increase in P-gp transport activity, thus suggesting a promising source of new P-gp inhibitors and activators, respectively. The obtained results highlight fiscalins with promising neuroprotective effects and with relevance for the synthesis of new derivatives for the treatment/prevention of ND.

Effect of Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones in the Virulence of Resistant Bacteria

“…These compounds can be found in terrestrial and marine organisms, mainly in fungi [19], and show promising antimicrobial activities, including antiviral, antifungal, and antibacterial properties [19]. Additionally, synthetic analogues reported by our group have been shown to have a neuroprotective capacity and potential as antimalarial agents [20][21][22].…”

“…These compounds can be found in terrestrial and marine organisms, mainly in fungi [19], and show promising antimicrobial activities, including antiviral, antifungal, and antibacterial properties [19]. Additionally, synthetic analogues reported by our group have been shown to have a neuroprotective capacity and potential as antimalarial agents [20][21][22]. Regarding glycine-derived alkaloids, glyantrypine (1, Figure 2) is one of the simplest molecules in the fumiquinazoline family, being derived from anthranilic acid, tryptophan, and glycine.…”

An In Vitro Evaluation of the Potential Neuroprotective Effects of Intranasal Lipid Nanoparticles Containing Astaxanthin Obtained from Different Sources: Comparative Studies

“…One of the pathological hallmarks of Parkinson's Disease is the loss of dopaminergic neurons in the substantia nigra pars compacta. To replicate this disease in vitro, the MPP + neurotoxin, the active metabolite of MPTP, is extensively used, as it is capable of severely damaging neuronal cells and inducing cell death, thus closely mimicking Parkinson's Disease [57][58][59]. MPP + is responsible for the inhibition of complex I of the mitochondrial electron transport chain, leading to ROS formation and ATP depletion, which changes the mitochondrial membrane potential and leads to apoptosis and the death of dopaminergic neurons [60,61].…”

“…MPP + is responsible for the inhibition of complex I of the mitochondrial electron transport chain, leading to ROS formation and ATP depletion, which changes the mitochondrial membrane potential and leads to apoptosis and the death of dopaminergic neurons [60,61]. Therefore, the cytotoxicity that is induced by MPP + has been frequently used to find the agents with potential neuroprotective effects [59].…”

Current Advances of Plant-Based Vaccines for Neurodegenerative Diseases

“…As a matter of fact, it has been projected that at least 70 million people will suffer from NDDs by 2030 and 106 million people will have them by 2050 [ 2 ]. NDDs belong to a heterogeneous group of incurable and debilitating human ailments distinguished by the progressive degeneration and/or the death of nerve cells of the central nervous system (CNS), which may result in motor, behavioral, and cognitive deficits [ 3 , 4 , 5 , 6 ]. Patients suffering from NDDs tend to experience impaired social functioning, depression, and sleep disorders [ 7 , 8 , 9 ], while the caregivers of these individuals might face social isolation, stress, burnout, and anxiety [ 7 ].…”